Molecules

268 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists

by Shuai Mu, Ying Liu, Min Gong, Deng-Ke Liu and Chang-Xiao Liu

Molecules 2014, 19(2), 2694-2706; https://doi.org/10.3390/molecules19022694 - 24 Feb 2014

Cited by 4 | Viewed by 7083

Abstract

Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by ¹H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo [...] Read more.

Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by ¹H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Characteristics, Composition and Oxidative Stability of Lannea microcarpa Seed and Seed Oil

by Patrice Bazongo, Imaël Henri Nestor Bassolé, Søren Nielsen, Adama Hilou, Mamoudou Hama Dicko and Vijai K. S. Shukla

Molecules 2014, 19(2), 2684-2693; https://doi.org/10.3390/molecules19022684 - 24 Feb 2014

Cited by 12 | Viewed by 8175

Abstract

The proximate composition of seeds and main physicochemical properties and thermal stability of oil extracted from Lannea microcarpa seeds were evaluated. The percentage composition of the seeds was: ash (3.11%), crude oil (64.90%), protein (21.14%), total carbohydrate (10.85%) and moisture (3.24%). Physicochemical properties [...] Read more.

The proximate composition of seeds and main physicochemical properties and thermal stability of oil extracted from Lannea microcarpa seeds were evaluated. The percentage composition of the seeds was: ash (3.11%), crude oil (64.90%), protein (21.14%), total carbohydrate (10.85%) and moisture (3.24%). Physicochemical properties of the oil were: refractive index, 1.473; melting point, 22.60°C; saponification value, 194.23 mg of KOH/g of oil; iodine value, 61.33 g of I₂/100 g of oil; acid value, 1.21 mg of KOH/g of oil; peroxide value, 1.48 meq of O₂/kg of oil and oxidative stability index, 43.20 h. Oleic (43.45%), palmitic (34.45%), linoleic (11.20%) and stearic (8.35%) acids were the most dominant fatty acids. Triacylglycerols with equivalent carbon number (ECN) 48 and ECN 46 were dominant (46.96% and 37.31%, respectively). The major triacylglycerol constituents were palmitoyl diolein (POO) (21.23%), followed by dipalmitoyl olein (POP) (16.47%), palmitoyl linoleyl olein (PLO) (12.03%), dipalmitoyl linolein (PLP) (10.85%) and dioleoyl linolein (LOO) (9.30%). The total polyphenol and tocopherol contents were 1.39 mg GAE g⁻¹ DW and 578.56 ppm, respectively. γ-Tocopherol was the major tocopherol (437.23 ppm). These analytical results indicated that the L. microcarpa seed oil could be used as a frying oil and in the cosmetic industry. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Comparative Diagnostic Techniques for Cryptosporidium Infection

by Beauty E. Omoruyi, Uchechukwu U. Nwodo, Chukwuneke S. Udem and Francis O. Okonkwo

Molecules 2014, 19(2), 2674-2683; https://doi.org/10.3390/molecules19022674 - 24 Feb 2014

Cited by 26 | Viewed by 14553

Abstract

Diarrhoea caused by Cryptosporidium is usually mild in immune competent individuals but severe in the young and those with underlying disease leading to compromised immunity. The conventional diagnosis of Cryptosporidium requires observation of the infective oocysts however, their tiny size yields indistinct results, [...] Read more.

Diarrhoea caused by Cryptosporidium is usually mild in immune competent individuals but severe in the young and those with underlying disease leading to compromised immunity. The conventional diagnosis of Cryptosporidium requires observation of the infective oocysts however, their tiny size yields indistinct results, thus limiting the effectiveness of the conventional diagnostic technique, modified Ziehl-Neelsen (ZN) differential staining. Consequent to the abovementioned limitation, ZN staining, sandwich antigen detection enzyme linked immunosorbent assay (sad-ELISA) and a direct polymerase chain reaction (PCR) assay techniques were evaluated for diagnostic efficacy. Stool samples were collected from 180 consenting adult patients attending outpatient and inpatient clinics at Victoria Hospital, Alice, Eastern Cape Province of South Africa. Subjects were stratified as; 35 HIV-positive and diarrhoeagenic, 125 HIV-negative diarrhoeagenic and 20 apparently healthy controls. Cryptosporidium incidence following diagnostic techniques were 13 (37.1%; ZN staining), 26 (74.3%; sad-ELISA) and 23 (65.7%; PCR), respectively, among HIV-positive diarrhoeagenic patients and 34 (27.2%; ZN staining), 96 (76.8%; sad-ELISA) and 89 (71.2%; PCR) among HIV-negative diarrhoeagenic patients. Sensitivity, specificity and predictive values of the diagnostic techniques’ efficiency were: sensitivity: 46.2% (HIV-positive) and 32.3% (HIV-negative) against the ZN technique and 96.9% against sad-ELISA and PCR, respectively, for both HIV-positive and -negative patients; specificity was 88.9% (HIV-positive) and 96.6% (HIV-negative) against the ZN technique. Lastly, the predictive values were 92.3% (HIV-positive) and 96.9% (HIV-negative), respectively, following ZN staining. The sad-ELISA technique proved more suitable for the determination of the presence of Cryptosporidium oocysts. The high incidence of Cryptosporidium in HIV-positive subjects as compared to the HIV-negative population accentuates the significance of cryptosporidiosis diagnosis in the treatment and management of HIV cases. Full article

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Open AccessArticle

Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

by Wei Zhang, Jing Ai, Dakuo Shi, Xia Peng, Yinchun Ji, Jian Liu, Meiyu Geng and Yingxia Li

Molecules 2014, 19(2), 2655-2673; https://doi.org/10.3390/molecules19022655 - 24 Feb 2014

Cited by 7 | Viewed by 7231

Abstract

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on [...] Read more.

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC₅₀ values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC₅₀s ranging from 0.57−16 μM. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Synthesis of A New Class of Pyridazin-3-one and 2-Amino-5-arylazopyridine Derivatives and Their Utility in the Synthesis of Fused Azines

by Hamada Mohamed Ibrahim and Haider Behbehani

Molecules 2014, 19(2), 2637-2654; https://doi.org/10.3390/molecules19022637 - 24 Feb 2014

Cited by 15 | Viewed by 7431

Abstract

A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives [...] Read more.

A general route for the synthesis of a novel class of pyridazin-3-one derivatives 3 by the reaction in acetic anhydride between 3-oxo-2-arylhydrazonopropanals 1 and some active methylene compounds like p-nitrophenylacetic acid and cyanoacetic acid was established. Under these conditions the pyridazin-3-one derivatives 3 were formed as the sole isolable products in excellent yield. The 6-acetyl-3-oxopyridazine derivative 3l was reacted with DMF-DMA to afford the corresponding enaminone derivative 4, which reacts with a variety of aminoazoles to afford the corresponding azolo[1,5-a]pyrimidine derivatives 5–7. Also, in order to explore the viability and generality of a recently uncovered reaction between 3-oxo-2-arylhydrazonopropanals and active methylene compounds, a variety of 2-amino-6-aryl-5-arylazo-3-aroylpyridines 16–19 were prepared by reacting 3-oxo-2-arylhydrazonopropanals with miscellaneous active methylene compounds like 3-oxo-3-phenylpropionitrile, hetaroylacetonitriles and cyanoacetamides. These 2-aminopyridine derivatives undergo smooth reactions with cyanoacetic acid that led to the formation in high yield of a new class of 1,8-naphthyridine derivatives 24. The structures of all new substances prepared in this investigation were determined by the different analytical spectroscopic methods, in addition to the X-ray crystallographic analysis. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Three New Tetranorditerpenes from Aerial Parts of Acerola Cherry (Malpighia emarginata)

by Jie-Qing Liu, Yuan-Yuan Deng, Ting-Zhao Li, Qiang Han, Yan Li and Ming-Hua Qiu

Molecules 2014, 19(2), 2629-2636; https://doi.org/10.3390/molecules19022629 - 24 Feb 2014

Cited by 12 | Viewed by 7206

Abstract

Acerola cherry is a world famous fruit which contains abundant antioxidants such as vitamin C, anthocyanins, flavonoids, and phenolics. However, studies concerning bioactivity components from aerial parts of acerola (Malpighia emarginata) are scarce. In view of this, we have examined the [...] Read more.

Acerola cherry is a world famous fruit which contains abundant antioxidants such as vitamin C, anthocyanins, flavonoids, and phenolics. However, studies concerning bioactivity components from aerial parts of acerola (Malpighia emarginata) are scarce. In view of this, we have examined the constituents of aerial parts of acerola, and three new tetranorditerpenes acerolanins A–C (1–3) with a rare 2H-benz[e]inden-2-one substructure were isolated. Their structures were determined on the basis of spectral studies and acerolanin C was confirmed by X-ray crystallographic analysis. Furthermore, three new compounds have been studied for their cytotoxic activity. Full article

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Open AccessArticle

Triptolide Induces S Phase Arrest and Apoptosis in Gallbladder Cancer Cells

by Yun-Ping Hu, Zhu-Jun Tan, Xiang-Song Wu, Tian-Yu Liu, Lin Jiang, Run-Fa Bao, Yi-Jun Shu, Mao-Lan Li, Hao Weng, Qian Ding, Feng Tao and Ying-Bin Liu

Molecules 2014, 19(2), 2612-2628; https://doi.org/10.3390/molecules19022612 - 24 Feb 2014

Cited by 24 | Viewed by 8179

Abstract

Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first [...] Read more.

Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first time we investigated the effects of triptolide on gallbladder cancer cells and identified the mechanisms underlying its potential anticancer effects. The MTT assay showed that triptolide decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that triptolide strongly suppressed colony formation ability in GBC-SD and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S phase arrest in gallbladder cancer cells. In addition, triptolide induced apoptosis, as shown by the results of annexin V/propidium iodide double-staining and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Finally, western blot analysis of triptolide-treated cells revealed the activation of caspase-3, caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that triptolide may be a promising drug to treat gallbladder carcinoma. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Glycosylation of a Newly Functionalized Orthoester Derivative

by Kohei Kawa, Tsuyoshi Saitoh, Eisuke Kaji and Shigeru Nishiyama

Molecules 2014, 19(2), 2602-2611; https://doi.org/10.3390/molecules19022602 - 24 Feb 2014

Cited by 1 | Viewed by 6364

Abstract

Tandem glycosylation of the 6-O-Fmoc-substituted benzyl orthoester derivative 2a was carried out in moderate yields by electrogenerated acid (EGA). The Fmoc group was effectively removed under mild basic conditions, and the product was submitted to the subsequent glycosylation. Full article

(This article belongs to the Section Organic Chemistry)

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1637 KiB

Open AccessArticle

Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents

by Seetha Ramasamy, Lik Voon Kiew and Lip Yong Chung

Molecules 2014, 19(2), 2588-2601; https://doi.org/10.3390/molecules19022588 - 24 Feb 2014

Cited by 39 | Viewed by 11500

Abstract

Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the [...] Read more.

Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited non-competitive inhibition of CYP2C19 (IC₅₀/Ki = 23.67/9.5 µg/mL), CYP2C9 (36.49/12.5 µg/mL), CYP1A2 (52.20/25.1 µg/mL); competitive inhibition of CYP3A4 (83.95/14.5 µg/mL) and weak inhibition of CYP2D6 (IC₅₀ = 2061.50 µg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 µg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro

by René Chofor, Martijn D.P. Risseeuw, Jenny Pouyez, Chinchu Johny, Johan Wouters, Cynthia S. Dowd, Robin D. Couch and Serge Van Calenbergh

Molecules 2014, 19(2), 2571-2587; https://doi.org/10.3390/molecules19022571 - 24 Feb 2014

Cited by 15 | Viewed by 7761

Abstract

Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or [...] Read more.

Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that identifying effective alternative bidentate ligands for this target enzyme is challenging. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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Open AccessArticle

Synthesis, Spectroscopic and Theoretical Studies of New Quasi-Podands from Bile Acid Derivatives Linked by 1,2,3-Triazole Rings

by Tomasz Pospieszny, Hanna Koenig, Iwona Kowalczyk and Bogumił Brycki

Molecules 2014, 19(2), 2557-2570; https://doi.org/10.3390/molecules19022557 - 24 Feb 2014

Cited by 18 | Viewed by 8564

Abstract

A novel method for the synthesis of bile acid derivatives has been developed using “click chemistry”. Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products [...] Read more.

A novel method for the synthesis of bile acid derivatives has been developed using “click chemistry”. Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products were confirmed by spectral (¹H-NMR, ¹³C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods. Estimation of the pharmacotherapeutic potential has been accomplished for synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS). Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

In Vivo and In Vitro Anti-Tumor Effects of Fungal Extracts

by Hung-Tsung Wu, Feng-Hwa Lu, Yu-Chu Su, Horng-Yih Ou, Hao-Chang Hung, Jin-Shang Wu, Yi-Ching Yang and Chih-Jen Chang

Molecules 2014, 19(2), 2546-2556; https://doi.org/10.3390/molecules19022546 - 21 Feb 2014

Cited by 43 | Viewed by 9373

Abstract

Fungal extracts are extensively used as nutritional supplements in Far-Eastern Asia. In this study, we aimed to evaluate the anti-cancer activities of some different fungal species against different cancer cell lines. The water or ethanol extracts of Fomitopsis pinicola (F. pinicola), [...] Read more.

Fungal extracts are extensively used as nutritional supplements in Far-Eastern Asia. In this study, we aimed to evaluate the anti-cancer activities of some different fungal species against different cancer cell lines. The water or ethanol extracts of Fomitopsis pinicola (F. pinicola), Ganoderma sinense, Fomitopsis officinalis, Polyporus melanopus, and Taiwanofungus camphorates were used to evaluate the anti-cancer activities in various cancer cells. We found that all of the fungi ethanol extracts used in this study exert anti-cancer activities in vitro, whereas water extracts show lower inhibitory activities as determined by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Among the tested fungi species, F. pinicola ethanol extract exerts the most significant anti-cancer activity (growth inhibitory ratio 82.8%, p < 0.001) by increasing cell apoptosis. Moreover, F. pinicola ethanol extract significantly decreased tumor size (tumor growth inhibitory ratio 54%, p < 0.05) and increased the lifespan in mice bearing sarcoma-180 tumors. Taken together, this is the first study indicating the anti-tumor effect of F. pinicola in vivo and in vitro. F. pinicola ethanol extract induces cell apoptosis to exert a significant anti-tumor activity, with potential to be a new alternative anti-tumor medicine. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessCommunication

Skullcap (Scutellaria baicalensis) Extract and Its Active Compound, Wogonin, Inhibit Ovalbumin-Induced Th2-Mediated Response

by Hee Soon Shin, Min-Jung Bae, Dae Woon Choi and Dong-Hwa Shon

Molecules 2014, 19(2), 2536-2545; https://doi.org/10.3390/molecules19022536 - 21 Feb 2014

Cited by 32 | Viewed by 9195

Abstract

Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex [...] Read more.

Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex vivo and in vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for analyses of cytokine production and cell viability. Mice sensitized with OVA were orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig) and cytokine levels were measured by enzyme-linked immunosorbent assays. Treatment with skullcap significantly inhibited interleukin (IL)-4 production without reduction of cell viability. Moreover, wogonin, but not baicalin and baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5 prediction. Wogonin as an active component of skullcap may be applied as a therapeutic agent for IgE- and IL-5-mediated allergic disorders. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

by Mariano Walter Pertino, Valery Verdugo, Cristina Theoduloz and Guillermo Schmeda-Hirschmann

Molecules 2014, 19(2), 2523-2535; https://doi.org/10.3390/molecules19022523 - 21 Feb 2014

Cited by 30 | Viewed by 6793

Abstract

Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid), and its alcohol dehydroabietinol [...] Read more.

Dehydroabietic acid (DHA) is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid), and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol), four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells. Better antiproliferative effect was found for compound 5, with an IC₅₀ of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC₅₀ of etoposide, was 1.83 µM. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Effects of Honey and Its Mechanisms of Action on the Development and Progression of Cancer

by Omotayo O. Erejuwa, Siti A. Sulaiman and Mohd S. Ab Wahab

Molecules 2014, 19(2), 2497-2522; https://doi.org/10.3390/molecules19022497 - 21 Feb 2014

Cited by 134 | Viewed by 41385

Abstract

Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available [...] Read more.

Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent) with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Pharmacophore Generation from a Drug-like Core Molecule Surrounded by a Library Peptide via the 10BASE_d-T on Bacteriophage T7

by Yuuki Tokunaga, Yuuki Azetsu, Keisuke Fukunaga, Takaaki Hatanaka, Yuji Ito and Masumi Taki

Molecules 2014, 19(2), 2481-2496; https://doi.org/10.3390/molecules19022481 - 21 Feb 2014

Cited by 5 | Viewed by 11611

Abstract

We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASE_d-T) undergoes almost quantitatively like a click reaction without side reaction or loss [...] Read more.

We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASE_d-T) undergoes almost quantitatively like a click reaction without side reaction or loss of phage infectivity. The post-translational modification yield, as well as the site-specificity, is quantitatively analyzed by a fluorescent densitometric analysis after gel electrophoresis. The detailed structure of the modified peptide on phage is identified with tandem mass spectrometry. Construction of such a peptide-fused phage library possessing non-natural core structures will be useful for future drug discovery. For this aim, we propose a novel concept of pharmacophore generation from a drug-like molecule (i.e., salicylic acid) conjugated with surrounding randomized peptides. By using the hybrid library, streptavidin-specific binders are isolated through four rounds of biopanning. Full article

(This article belongs to the Special Issue Bioorthogonal Chemistry)

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Open AccessArticle

Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

by Peng Wang, Hui-Hui Yuan, Xue Zhang, Yun-Ping Li, Lu-Qing Shang and Zheng Yin

Molecules 2014, 19(2), 2469-2480; https://doi.org/10.3390/molecules19022469 - 21 Feb 2014

Cited by 38 | Viewed by 8218

Abstract

Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including [...] Read more.

Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated that compounds bearing diverse amine substituents at the C-2 position demonstrated good anticancer activities. The selectivity towards different cancer cell lines of the synthesized derivatives is discussed. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessReview

Clinical Application of MicroRNA Testing in Neuroendocrine Tumors of the Gastrointestinal Tract

by Caterina Vicentini, Matteo Fassan, Edoardo D'Angelo, Vincenzo Corbo, Nicola Silvestris, Gerard J. Nuovo and Aldo Scarpa

Molecules 2014, 19(2), 2458-2468; https://doi.org/10.3390/molecules19022458 - 21 Feb 2014

Cited by 46 | Viewed by 9692

Abstract

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal [...] Read more.

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal tumors including gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs are a heterogeneous group of epithelial neoplasms with neuroendocrine differentiation. At present, early detection and surgical resection of GEP-NETs represent the best chance for a cure. Thus, clinically useful biomarkers for GEP-NETs that strongly correlate with early detection are urgently needed. The purpose of this review is to summarize the role of miRNAs in GEP-NET carcinogenesis and their possible use as novel diagnostic, prognostic and predictive biomarkers. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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Open AccessArticle

Preparation and In Vitro Evaluation of Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carriers

by Yang Chu, Dan Li, Yi-Fan Luo, Xiao-Jin He and Ming-Yan Jiang

Molecules 2014, 19(2), 2445-2457; https://doi.org/10.3390/molecules19022445 - 21 Feb 2014

Cited by 30 | Viewed by 9503

Abstract

Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a [...] Read more.

Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carrier (Cur-GA-PEG-NLC) was prepared by the film ultrasound method to improve the tumor-targeting ability. The drug content was detected by an UV spectrophotometry method. The encapsulation efficiency of curcumin in the nanostructured lipid carriers (NLCs) was determined using a mini-column centrifugation method. The encapsulation efficiency for various Cur-GA-PEG-NLC was within the range of 90.06%–95.31% and particle size was between 123.1 nm and 132.7 nm. An in vitro MTT assay showed that Cur-GA10%-PEG-NLC had significantly high cellular uptake and cytotoxicity against HepG2 cells compared with other groups. Full article

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Open AccessArticle

A Tractable and Efficient One-Pot Synthesis of 5'-Azido-5'-deoxyribonucleosides

by Theodore V. Peterson, Tobin U. B. Streamland and Ahmed M. Awad

Molecules 2014, 19(2), 2434-2444; https://doi.org/10.3390/molecules19022434 - 21 Feb 2014

Cited by 7 | Viewed by 8030

Abstract

Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine, guanosine, and uridine, resulting in a widely applicable one-pot methodology for the synthesis of these and related compounds. The target compounds are appropriate as precursors in a variety of purposive syntheses, as the synthetic [...] Read more.

Synthetic routes to 5'-azidoribonucleosides are reported for adenosine, cytidine, guanosine, and uridine, resulting in a widely applicable one-pot methodology for the synthesis of these and related compounds. The target compounds are appropriate as precursors in a variety of purposive syntheses, as the synthetic and therapeutic relevance of azido- and amino-modified nucleosides is expansive. Furthermore, in the conversion of alcohols to azides, these methods offer a tractable alternative to the Mitsunobu and other more difficult reactions. Full article

(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)

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2665 KiB

Open AccessReview

Ultrafast Internal Conversion of Aromatic Molecules Studied by Photoelectron Spectroscopy using Sub-20 fs Laser Pulses

by Toshinori Suzuki

Molecules 2014, 19(2), 2410-2433; https://doi.org/10.3390/molecules19022410 - 21 Feb 2014

Cited by 7 | Viewed by 9271

Abstract

This article describes our recent experimental studies on internal conversion via a conical intersection using photoelectron spectroscopy. Ultrafast S₂(ππ*)–S₁(nπ*) internal conversion in pyrazine is observed in real time using sub-20 fs deep ultraviolet pulses [...] Read more.

This article describes our recent experimental studies on internal conversion via a conical intersection using photoelectron spectroscopy. Ultrafast S₂(ππ*)–S₁(nπ*) internal conversion in pyrazine is observed in real time using sub-20 fs deep ultraviolet pulses (264 and 198 nm). While the photoelectron kinetic energy distribution does not exhibit a clear signature of internal conversion, the photoelectron angular anisotropy unambiguously reveals the sudden change of electron configuration upon internal conversion. An explanation is presented as to why these two observables have different sensitivities to internal conversion. The 198 nm probe photon energy is insufficient for covering the entire Franck-Condon envelopes upon photoionization from S₂/S₁ to D₁/D₀. A vacuum ultraviolet free electron laser (SCSS) producing 161 nm radiation is employed to solve this problem, while its pulse-to-pulse timing jitter limits the time resolution to about 1 ps. The S₂–S₁ internal conversion is revisited using the sub-20 fs 159 nm pulse created by filamentation four-wave mixing. Conical intersections between D₁(π⁻¹) and D₀(n⁻¹) and also between the Rydberg state with a D₁ ion core and that with a D₀ ion core of pyrazine are studied by He(I) photoelectron spectroscopy, pulsed field ionization photoelectron spectroscopy and one-color resonance-enhanced multiphoton ionization spectroscopy. Finally, ultrafast S₂(ππ*)–S₁(ππ*) internal conversion in benzene and toluene are compared with pyrazine. Full article

(This article belongs to the Special Issue Photoelectron Spectroscopy)

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2333 KiB

Open AccessArticle

Endotoxin Molecule Lipopolysaccharide-Induced Zebrafish Inflammation Model: A Novel Screening Method for Anti-Inflammatory Drugs

by Li-Ling Yang, Guo-Quan Wang, Li-Mei Yang, Zhi-Bing Huang, Wen-Qing Zhang and Lin-Zhong Yu

Molecules 2014, 19(2), 2390-2409; https://doi.org/10.3390/molecules19022390 - 21 Feb 2014

Cited by 101 | Viewed by 15520

Abstract

Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties [...] Read more.

Lipopolysaccharide (LPS), an endotoxin molecule, has been used to induce inflammatory responses. In this study, LPS was used to establish an in vivo inflammation model in zebrafish for drug screening. We present an experimental method that conveniently and rapidly assesses the anti-inflammatory properties of drugs. The yolks of 3-day post-fertilization (dpf) larvae were injected with 0.5 mg/mL LPS to induce fatal inflammation. After LPS stimulation, macrophages were tracked by NR and SB staining and neutrophil migration was observed using the MPO:GFP line. Larval mortality was used as the primary end-point. Expression levels of key cytokines involved in the inflammatory response including IL-1β, IL-6, and TNF-α, were measured using quantitative reverse transcription polymerase chain reaction (RT-PCR). Macrophages and neutrophils were both recruited to the LPS-injected site during the inflammatory response. Mortality was increased by LPS in a dose-dependent manner within 48 h. Analyses of IL-1β, IL-6, and TNF-α expression levels revealed the upregulation of the inflammatory response in the LPS-injected larvae. Further, the anti-inflammatory activity of chlorogenic acid (CA) was evaluated in this zebrafish model to screen for anti-inflammatory drugs. A preliminary result showed that CA revealed a similar effect as the corticosteroid dexamethasone (DEX), which was used as a positive control, by inhibiting macrophage and neutrophil recruitment to the LPS site and improving survival. Our results suggest that this zebrafish screening model could be applied to study inflammation-mediated diseases. Moreover, the Traditional Chinese Medicine CA displays potential anti-inflammatory activity. Full article

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Open AccessArticle

Functional Properties of a Cysteine Proteinase from Pineapple Fruit with Improved Resistance to Fungal Pathogens in Arabidopsis thaliana

by Wei Wang, Lu Zhang, Ning Guo, Xiumei Zhang, Chen Zhang, Guangming Sun and Jianghui Xie

Molecules 2014, 19(2), 2374-2389; https://doi.org/10.3390/molecules19022374 - 21 Feb 2014

Cited by 19 | Viewed by 8766

Abstract

In plant cells, many cysteine proteinases (CPs) are synthesized as precursors in the endoplasmic reticulum, and then are subject to post-translational modifications to form the active mature proteinases. They participate in various cellular and physiological functions. Here, AcCP2, a CP from pineapple fruit [...] Read more.

In plant cells, many cysteine proteinases (CPs) are synthesized as precursors in the endoplasmic reticulum, and then are subject to post-translational modifications to form the active mature proteinases. They participate in various cellular and physiological functions. Here, AcCP2, a CP from pineapple fruit (Ananas comosus L.) belonging to the C1A subfamily is analyzed based on the molecular modeling and homology alignment. Transcripts of AcCP2 can be detected in the different parts of fruits (particularly outer sarcocarps), and gradually increased during fruit development until maturity. To analyze the substrate specificity of AcCP2, the recombinant protein was overexpressed and purified from Pichia pastoris. The precursor of purified AcCP2 can be processed to a 25 kDa active form after acid treatment (pH 4.3). Its optimum proteolytic activity to Bz-Phe-Val-Arg-NH-Mec is at neutral pH. In addition, the overexpression of AcCP2 gene in Arabidopsis thaliana can improve the resistance to fungal pathogen of Botrytis cinerea. These data indicate that AcCP2 is a multifunctional proteinase, and its expression could cause fruit developmental characteristics of pineapple and resistance responses in transgenic Arabidopsis plants. Full article

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Open AccessArticle

Edge-Termination and Core-Modification Effects of Hexagonal Nanosheet Graphene

by Jin-Pei Deng, Wen-Hao Chen, Shou-Po Chiu, Chih-Hsun Lin and Bo-Cheng Wang

Molecules 2014, 19(2), 2361-2373; https://doi.org/10.3390/molecules19022361 - 21 Feb 2014

Cited by 22 | Viewed by 7790

Abstract

Optimized geometries and electronic structures of two different hexagonal grapheme nanosheets (HGNSs), with armchair (n-A-HGNS, n = 3–11) and zigzag (n-Z-HGNS, n = 1–8) edges have been calculated by using the GGA/PBE method implemented in the SIESTA package, with [...] Read more.

Optimized geometries and electronic structures of two different hexagonal grapheme nanosheets (HGNSs), with armchair (n-A-HGNS, n = 3–11) and zigzag (n-Z-HGNS, n = 1–8) edges have been calculated by using the GGA/PBE method implemented in the SIESTA package, with the DZP basis set, where n represents the number of peripheral rings. The computed HOMO-LUMO energy gap (E_g = E_LUMO − E_HOMO) decreases for fully H-terminated A- and Z-HGNSs with increasing n, i.e., with increasing nanosheet size and p_π-orbitals being widely delocalized over the sheet surface. The full terminations, calculated with various functional groups, including the electron-withdrawing (F-, Cl-, and CN-) and -donating (OH-, and SH-) substitutions, were addressed. Significant lowering of E_HOMO and E_LUMO was obtained for CN-terminated HGNS as compared to those for H-terminated ones due to the mesomeric effect. The calculated E_g value decreases with increasing n for all terminations, whereby for the SH-termination in HGNS, the termination effect becomes less significant with increasing n. Further, the calculation results for stabilities of HGNS oxides support the tendency toward the oxidative reactivity at the edge site of the sheet, which shows most pronounced C-C bond length alternation, by chemical modification. Physical properties of HGNSs with various numbers of the core-defects, which can be obtained by strong oxidation, were also investigated. Their structures can change drastically from planar to saddle-like shapes. These conformations could be used as stationary phases with controlled interaction in the separation methods such as HPLC and the other chemical analysis techniques. Full article

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Open AccessArticle

Influence of Extractive Solvents on Lipid and Fatty Acids Content of Edible Freshwater Algal and Seaweed Products, the Green Microalga Chlorella kessleri and the Cyanobacterium Spirulina platensis

by Jarmila Vavra Ambrozova, Ladislava Misurcova, Robert Vicha, Ludmila Machu, Dusan Samek, Mojmir Baron, Jiri Mlcek, Jiri Sochor and Tunde Jurikova

Molecules 2014, 19(2), 2344-2360; https://doi.org/10.3390/molecules19022344 - 21 Feb 2014

Cited by 39 | Viewed by 10137

Abstract

Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera, N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A; Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal [...] Read more.

Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera, N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A; Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal and cyanobacterial (Spirulina platensis, S) products, and autotrophically cultivated samples of the green microalga Chlorella kessleri (CK) and the cyanobacterium Spirulina platensis (SP) were determined using a solvent mixture of methanol/chloroform/water (1:2:1, v/v/v, solvent I) and n-hexane (solvent II). Total lipid contents ranged from 0.64% (II) to 18.02% (I) by dry weight and the highest total lipid content was observed in the autotrophically cultivated cyanobacterium Spirulina platensis. Solvent mixture I was found to be more effective than solvent II. Fatty acids were determined by gas chromatography of their methyl esters (% of total FAMEs). Generally, the predominant fatty acids (all results for extractions with solvent mixture I) were saturated palmitic acid (C16:0; 24.64%–65.49%), monounsaturated oleic acid (C18:1(n-9); 2.79%–26.45%), polyunsaturated linoleic acid (C18:2(n-6); 0.71%–36.38%), α-linolenic acid (C18:3(n-3); 0.00%–21.29%), γ-linolenic acid (C18:3(n-6); 1.94%–17.36%), and arachidonic acid (C20:4(n-6); 0.00%–15.37%). The highest content of ω-3 fatty acids (21.29%) was determined in Chlorella pyrenoidosa using solvent I, while conversely, the highest content of ω-6 fatty acids (41.42%) was observed in Chlorella kessleri using the same solvent. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Fatty Acids from Pool Lipids as Possible Precursors of the Male Marking Pheromone in Bumblebees

by Edita Kofroňová, Adam Nekola, Josef Cvačka, Jiří Kindl and Irena Valterová

Molecules 2014, 19(2), 2330-2343; https://doi.org/10.3390/molecules19022330 - 21 Feb 2014

Cited by 4 | Viewed by 6568

Abstract

Triacylglycerols (TGs) stored in the fat bodies of bumblebee males have a species-specific composition. The striking structural similarities between TG fatty acids (FAs) and components of the male marking pheromone in certain species led to the hypothesis that FAs may serve as precursors [...] Read more.

Triacylglycerols (TGs) stored in the fat bodies of bumblebee males have a species-specific composition. The striking structural similarities between TG fatty acids (FAs) and components of the male marking pheromone in certain species led to the hypothesis that FAs may serve as precursors in pheromone biosynthesis. Here, we analysed TGs from B. ruderatus, B. bohemicus, and B. campestris. Nonadec-9-ene and icos-15-en-1-ol are the main components of B. ruderatus labial gland secretion, forming up to 92% of the gland extract. The corresponding icos-11-enic and icos-15-enic acids were found in TGs at levels higher than usual for bumblebee species. We found similar relationships in B. campestris and B. bohemicus. These results suggest that FAs might be precursors of aliphatic compounds in the male pheromones. Furthermore, we report for the first time the pheromone structure of B. ruderatus males. Full article

(This article belongs to the Special Issue Fatty Acids)

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1717 KiB

Open AccessReview

Carnosinases, Their Substrates and Diseases

by Francesco Bellia, Graziella Vecchio and Enrico Rizzarelli

Molecules 2014, 19(2), 2299-2329; https://doi.org/10.3390/molecules19022299 - 21 Feb 2014

Cited by 82 | Viewed by 14470

Abstract

Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine) and homocarnosine (γ-aminobutyryl-L-histidine). Alterations of serum carnosinase (CN1) activity has been associated [...] Read more.

Carnosinases are Xaa-His dipeptidases that play diverse functions throughout all kingdoms of life. Human isoforms of carnosinase (CN1 and CN2) under appropriate conditions catalyze the hydrolysis of the dipeptides carnosine (β-alanyl-L-histidine) and homocarnosine (γ-aminobutyryl-L-histidine). Alterations of serum carnosinase (CN1) activity has been associated with several pathological conditions, such as neurological disorders, chronic diseases and cancer. For this reason the use of carnosinase levels as a biomarker in cerebrospinal fluid (CSF) has been questioned. The hydrolysis of imidazole-related dipeptides in prokaryotes and eukaryotes is also catalyzed by aminoacyl-histidine dipeptidases like PepD (EC 3.4.13.3), PepV (EC 3.4.13.19) and anserinase (EC 3.4.13.5). The review deals with the structure and function of this class of enzymes in physiological and pathological conditions. The main substrates of these enzymes, i.e., carnosine, homocarnosine and anserine (β-alanyl-3-methyl-L-histidine) will also be described. Full article

(This article belongs to the Special Issue Enzyme Chemistry)

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Open AccessArticle

Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding

by Katherine L. Hayden and David E. Graves

Molecules 2014, 19(2), 2286-2298; https://doi.org/10.3390/molecules19022286 - 21 Feb 2014

Cited by 6 | Viewed by 6544

Abstract

Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)_n is found at the ends of chromosomes and provides a novel target for the development of new drugs [...] Read more.

Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)_n is found at the ends of chromosomes and provides a novel target for the development of new drugs in the treatment of age related diseases such as cancer. These telomeric sequences show slight sequence variations from species to species; however, each contains repeats of 3 to 4 guanines allowing the G-rich strands to fold into compact and stable nuclease resistant conformations referred to as G-quadruplexes. The focus of this manuscript is to examine the effects of 5'-nucleotides flanking the human telomeric core sequence 5'-AGGG(TTAGGG) ₃-3' (h-Tel22). Our studies reveal that the addition of the 5'-flanking nucleotides (5'-T, and 5'-TT) results in significant changes to the thermodynamic stability of the G-quadruplex structure. Our data indicate that the observed changes in stability are associated with changes in the number of bound waters resulting from the addition of 5'-flanking nucleotides to the h-Tel22 sequence as well as possible intermolecular interactions of the 5' overhang with the core structure. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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1628 KiB

Open AccessArticle

On Tuning the Fluorescence Emission of Porphyrin Free Bases Bonded to the Pore Walls of Organo-Modified Silica

by Rosa I. Y. Quiroz-Segoviano, Iris N. Serratos, Fernando Rojas-González, Salvador R. Tello-Solís, Rebeca Sosa-Fonseca, Obdulia Medina-Juárez, Carmina Menchaca-Campos and Miguel A. García-Sánchez

Molecules 2014, 19(2), 2261-2285; https://doi.org/10.3390/molecules19022261 - 21 Feb 2014

Cited by 28 | Viewed by 9596

Abstract

A sol-gel methodology has been duly developed in order to perform a controlled covalent coupling of tetrapyrrole macrocycles (e.g., porphyrins, phthalocyanines, naphthalocyanines, chlorophyll, etc.) to the pores of metal oxide networks. The resulting absorption and emission spectra intensities in the UV-VIS-NIR range [...] Read more.

A sol-gel methodology has been duly developed in order to perform a controlled covalent coupling of tetrapyrrole macrocycles (e.g., porphyrins, phthalocyanines, naphthalocyanines, chlorophyll, etc.) to the pores of metal oxide networks. The resulting absorption and emission spectra intensities in the UV-VIS-NIR range have been found to depend on the polarity existing inside the pores of the network; in turn, this polarization can be tuned through the attachment of organic substituents to the tetrapyrrrole macrocycles before bonding them to the pore network. The paper shows clear evidence of the real possibility of maximizing fluorescence emissions from metal-free bases of substituted tetraphenylporphyrins, especially when these molecules are bonded to the walls of functionalized silica surfaces via the attachment of alkyl or aryl groups arising from the addition of organo-modified alkoxides. Full article

(This article belongs to the Special Issue Macrocyclic Chemistry)

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1632 KiB

Open AccessArticle

In Silico Studies of Quinoxaline-2-Carboxamide 1,4-di-N-Oxide Derivatives as Antimycobacterial Agents

by Awwad A. Radwan and Wael M. Abdel-Mageed

Molecules 2014, 19(2), 2247-2260; https://doi.org/10.3390/molecules19022247 - 21 Feb 2014

Cited by 15 | Viewed by 6327

Abstract

Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies [...] Read more.

Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular modeling study allowed us to confirm the preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives inside the active site. The obtained binding mode was as same as that of the novobiocin X-ray structure. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 19, Issue 2 (February 2014) – 85 articles , Pages 1378-2706

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