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Molecules, Volume 13, Issue 10 (October 2008) – 24 articles , Pages 2340-2703

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886 KiB  
Review
Biosynthesis and Genetic Regulation of Proanthocyanidins in Plants
by Fei He, Qiu-Hong Pan, Ying Shi and Chang-Qing Duan
Molecules 2008, 13(10), 2674-2703; https://doi.org/10.3390/molecules13102674 - 28 Oct 2008
Cited by 177 | Viewed by 24398
Abstract
Proanthocyanidins (PAs), also known as condensed tannins, are a group of polyphenolic secondary metabolites synthesized in plants as oligomers or polymers of flavan-3-ol units via the flavonoid pathway. Due to their structural complexity and varied composition, only in the recent years has the [...] Read more.
Proanthocyanidins (PAs), also known as condensed tannins, are a group of polyphenolic secondary metabolites synthesized in plants as oligomers or polymers of flavan-3-ol units via the flavonoid pathway. Due to their structural complexity and varied composition, only in the recent years has the study on the biosynthesis and regulation of PAs in plants taken off, although some details of the synthetic mechanism remain unclear. This paper aims to summarize the status of research on the structures of PAs in plants, the genes encoding key enzymes of biosynthetic pathway, the transport factors, the transcriptional regulation of PA biosynthesis and the genetic manipulation of PAs. The problems of this field were also discussed, including the nature of the final “enzyme” which catalyzes the polymerization reaction of PAs and the possible mechanism of how the elementary units of flavanols are assembled in vivo. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
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412 KiB  
Article
Overexpression of the Pdx-1 Homeodomain Transcription Factor Impairs Glucose Metabolism in Cultured Rat Hepatocytes
by Rudolf Tito Pillich, Gianfranco Scarsella and Gianfranco Risuleo
Molecules 2008, 13(10), 2659-2673; https://doi.org/10.3390/molecules13102659 - 28 Oct 2008
Cited by 2 | Viewed by 10558
Abstract
The Pdx-1 transcription factor plays crucial functions both during pancreas development and in the adult β cells. Previous studies have indicated that ectopic Pdx-1 expression in liver or intestinal primary and immortalized cells is sufficient to promote activation of insulin gene expression. This [...] Read more.
The Pdx-1 transcription factor plays crucial functions both during pancreas development and in the adult β cells. Previous studies have indicated that ectopic Pdx-1 expression in liver or intestinal primary and immortalized cells is sufficient to promote activation of insulin gene expression. This work is focused on the molecular and physiological consequences of Pdx-1 overexpression in liver cells. We present evidence that Pdx-1 affects the level of expression of one of the four mammalian hexokinase isozymes. These are glucose phosphorylating enzymes involved in essential cellular functions such as glucose sensing, metabolic energy production and apoptosis. Specifically, our data show that over-expression of Pdx-1 in cultured hepatocytes is able to repress the expression of hexokinase 2 (Hxk 2) and the phenomenon is mediated via binding of Pdx-1 to a specific sequence on the Hxk 2 gene promoter. As a consequence, liver cells over-expressing Pdx-1 present interesting alterations concerning glucose metabolism. Full article
(This article belongs to the Special Issue Nucleic Acids)
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192 KiB  
Communication
Diastereoselective Synthesis of Cyclopentanediols by InCl3/Al Mediated Intramolecular Pinacol Coupling Reaction in Aqueous Media
by Yunhua Chen, Jieping Wan, Chunyan Wang and Cuirong Sun
Molecules 2008, 13(10), 2652-2658; https://doi.org/10.3390/molecules13102652 - 27 Oct 2008
Cited by 6 | Viewed by 9816
Abstract
A “green” and practical intramolecular pinacol coupling reaction promoted by InCl3/Al catalysts in aqueous media has been developed. Under mild conditions, a novel class of polysubstituted cyclopentane-1,2-diols have been obtained with excellent diastereoselectivity. Full article
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330 KiB  
Review
Anti-carcinogenic Effects of the Flavonoid Luteolin
by Günter Seelinger, Irmgard Merfort, Ute Wölfle and Christoph M. Schempp
Molecules 2008, 13(10), 2628-2651; https://doi.org/10.3390/molecules13102628 - 22 Oct 2008
Cited by 295 | Viewed by 27200
Abstract
Luteolin is a flavonoid which is part of our daily nutrition in relatively low amounts (less than 1 mg/day). Nevertheless, some epidemiological studies suggest an inverse correlation between luteolin intake and the risk of some cancer types. Luteolin displays specific anti-inflammatory and anti-carcinogenic [...] Read more.
Luteolin is a flavonoid which is part of our daily nutrition in relatively low amounts (less than 1 mg/day). Nevertheless, some epidemiological studies suggest an inverse correlation between luteolin intake and the risk of some cancer types. Luteolin displays specific anti-inflammatory and anti-carcinogenic effects, which can only partly be explained by its anti-oxidant and free radical scavenging capacities. Luteolin can delay or block the development of cancer cells in vitro and in vivo by protection from carcinogenic stimuli, by inhibition of tumor cell proliferation, by induction of cell cycle arrest and by induction of apoptosis via intrinsic and extrinsic signaling pathways. When compared to other flavonoids, luteolin was usually among the most effective ones, inhibiting tumor cell proliferation with IC50 values between 3 and 50 μM in vitro and in vivo by 5 to 10 mg/kg i.p., intragastric application of 0.1–0.3 mg/kg/d, or as food additive in concentrations of 50 to 200 ppm. Luteolin has been shown to penetrate into human skin, making it also a candidate for the prevention and treatment of skin cancer. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
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462 KiB  
Article
Surface-enhanced Raman Spectral Measurements of 5-Fluorouracil in Saliva
by Stuart Farquharson, Alan Gift, Chetan Shende, Frank Inscore, Beth Ordway, Carl Farquharson and John Murren
Molecules 2008, 13(10), 2608-2627; https://doi.org/10.3390/molecules13102608 - 22 Oct 2008
Cited by 71 | Viewed by 16976
Abstract
The ability of surface-enhanced Raman spectroscopy (SERS) to measure 5-fluorouracil (5-FU) in saliva is presented. The approach is based on the capacity of Raman spectroscopy to provide a unique spectral signature for virtually every chemical, and the ability of SERS to provide μg/mL [...] Read more.
The ability of surface-enhanced Raman spectroscopy (SERS) to measure 5-fluorouracil (5-FU) in saliva is presented. The approach is based on the capacity of Raman spectroscopy to provide a unique spectral signature for virtually every chemical, and the ability of SERS to provide μg/mL sensitivity. A simple sampling method, that employed 1-mm glass capillaries filled with silver-doped sol-gels, was developed to isolate 5-FU from potential interfering chemical components of saliva and simultaneously provide SERSactivity. The method involved treating a 1 mL saliva sample with 1 mL of acetic acid, drawing 10 μL of sample into a SERS-active capillary by syringe, and then measuring the SER spectrum. Quality SER spectra were obtained for samples containing as little as 2 μg of 5-FU in 1 mL saliva. The entire process, the acid pretreatment, extraction and spectral measurement, took less than 5 minutes. The SERS of 5-fluorouridine and 5-fluoro-2’-deoxyuridine, two major metabolites of 5-FU, were also measured and shown to have unique spectral peaks. These measurements suggest that disposable SERS-active capillaries could be used to measure 5-FU and metabolite concentrations in chemotherapy patient saliva, thereby providing metabolic data that would allow regulating dosage. Tentative vibrational mode assignments for 5-FU and its metabolites are also given. Full article
(This article belongs to the Special Issue 5-Fluorouracil)
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158 KiB  
Article
The Synthesis of 1-(4-Triethoxysilyl)phenyl)-4,4,4-trifluoro-1,3-butanedione, a Novel Trialkoxysilane Monomer for the Preparation of Functionalized Sol-gel Matrix Materials
by Christopher J. Peeples, Raghu Ram Earni and John C. DiCesare
Molecules 2008, 13(10), 2601-2607; https://doi.org/10.3390/molecules13102601 - 20 Oct 2008
Cited by 1 | Viewed by 9178
Abstract
The title compound, 1-(4-triethoxysilyl)phenyl)-4,4,4-trifluoro-1,3-butanedione, was synthesized in a three-step sequence starting from 2-(4-bromophenyl)propene. Containing both a trialkoxysilyl and a substituted 1,3-butanedione functional grouping within its structure, this new silane is a viable starting material for the preparation of functionalized sol-gel materials. Full article
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405 KiB  
Review
Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products
by Sylvain Favre, Pierre Vogel and Sandrine Gerber-Lemaire
Molecules 2008, 13(10), 2570-2600; https://doi.org/10.3390/molecules13102570 - 17 Oct 2008
Cited by 60 | Viewed by 19067
Abstract
Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, [...] Read more.
Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect. Full article
(This article belongs to the Special Issue Spiro Compounds)
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243 KiB  
Article
Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H)-one Derivatives
by Hanan Georgey, Nagwa Abdel-Gawad and Safinaz Abbas
Molecules 2008, 13(10), 2557-2569; https://doi.org/10.3390/molecules13102557 - 16 Oct 2008
Cited by 102 | Viewed by 11066
Abstract
A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity [...] Read more.
A number of 3-substituted-2-(substituted-phenoxymethyl) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity. Full article
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515 KiB  
Article
Evaluation of the Antioxidant Activity of Syzygium cumini Leaves
by Zhi Ping Ruan, Liang Liang Zhang and Yi Ming Lin
Molecules 2008, 13(10), 2545-2556; https://doi.org/10.3390/molecules13102545 - 16 Oct 2008
Cited by 119 | Viewed by 21387
Abstract
The antioxidant activity of Syzygium cumini leaf extracts was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging and ferric-reducing antioxidant power (FRAP) assays. The methanolic extract and its four water, ethyl acetate, chloroform, and n-hexane fractions were prepared and subjected to antioxidant evaluation. [...] Read more.
The antioxidant activity of Syzygium cumini leaf extracts was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging and ferric-reducing antioxidant power (FRAP) assays. The methanolic extract and its four water, ethyl acetate, chloroform, and n-hexane fractions were prepared and subjected to antioxidant evaluation. The results showed that the ethyl acetate fraction had stronger antioxidant activity than the other ones. HPLC data indicated that S. cumini leaf extracts contained phenolic compounds, such as ferulic acid and catechin, responsible for their antioxidant activity. A significant linear relationship between antioxidant potency, free radical-scavenging ability and the content of phenolic compounds of leaf extracts supported this observation. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
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298 KiB  
Review
Advances of Modern Chromatographic and Electrophoretic Methods in Separation and Analysis of Flavonoids
by E-Hu Liu, Lian-Wen Qi, Jun Cao, Ping Li, Chang-Yin Li and Yong-Bo Peng
Molecules 2008, 13(10), 2521-2544; https://doi.org/10.3390/molecules13102521 - 16 Oct 2008
Cited by 56 | Viewed by 18733
Abstract
Flavonoids, one of the largest groups of secondary metabolites, are widespread in vegetable crops such as herbs, fruits, vegetables, grains, seeds and derived foods such as juices, wines, oils, etc. They receive considerable attention due to their biological and physiological importance. Hundreds [...] Read more.
Flavonoids, one of the largest groups of secondary metabolites, are widespread in vegetable crops such as herbs, fruits, vegetables, grains, seeds and derived foods such as juices, wines, oils, etc. They receive considerable attention due to their biological and physiological importance. Hundreds of publications on the analysis of flavonoids have appeared over the past decade. Traditional and more advanced techniques have come to prominence for sample preparation, separation, detection, and identification. This review intends to provide an updated, concise overview on the recent development and trends of separation, identification and quantification for flavonoids by modern chromatographic and spectrophotometric analytical techniques, including gas chromatography (GC), liquid chromatography (LC), and capillary electrophoresis (CE). The sample preparation before analysis is also briefly summarized. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
186 KiB  
Article
The Effect of Ginkgo Biloba (EGb 761) on Epileptic Activity in Rabbits
by Vesna Ivetic, Mira Popovic, Nada Naumovic, Mirjana Radenkovic and Vesna Vasic
Molecules 2008, 13(10), 2509-2520; https://doi.org/10.3390/molecules13102509 - 16 Oct 2008
Cited by 12 | Viewed by 11456
Abstract
Different animal models are used to evaluate the process of epileptogenesis. In this investigation the kindling model of epilepsy was used. The epileptic focus was induced in Chinchilla rabbits by stimulation of the hippocampus with electric stimuli. We presumed that the extracts of [...] Read more.
Different animal models are used to evaluate the process of epileptogenesis. In this investigation the kindling model of epilepsy was used. The epileptic focus was induced in Chinchilla rabbits by stimulation of the hippocampus with electric stimuli. We presumed that the extracts of Ginkgo biloba affect the formation of kindling epilepsy. Bioelectric activity of the brain was registered throughout the development of kindling with and without standardized extracts from dried ginkgo leaves (EGb 761). For each animal the following has been determined: the values of the minimum current strength necessary for the origination of threshold after-discharge (AD) – discharges appearing after the cessation of stimulation; duration of the threshold AD; number of stimulations necessary for the origination of full kindling; time latency for the development of full kindling; number of spontaneous epileptogenic discharges manifested in EEG two days following the formation of full kindling during 60-minute registration. The results show that the process of epileptogenesis was influenced by EGb 761. It has been established that if the animals received EGb 761, significantly weaker minimum current strength was necessary for the development of the epileptogenic focus and the AD were longer, while the number of necessary electrostimulations for the appearance of full kindling was less and the latency was shorter. Full article
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214 KiB  
Article
Two New Phenolic Glycosides from Viscum articulatum
by Yang Li, Yan-Li Zhao, Ning Huang, Yong-Tang Zheng, Yong-Ping Yang and Xiao-Li Li
Molecules 2008, 13(10), 2500-2508; https://doi.org/10.3390/molecules13102500 - 15 Oct 2008
Cited by 20 | Viewed by 12334
Abstract
Two new phenolic glycosides, 1-O-benzyl-[5-O-benzoyl-β-D-apiofuranosyl (1→2)]-β-D-glucopyranoside (1), and 4`-hydroxy-7,3`-dimethoxyflavan-5-O- β-D-gluco-pyranoside (2), together with nine known flavanones 3 - 11, have been isolated from the dried whole plants of Viscum articulatum.Their structures [...] Read more.
Two new phenolic glycosides, 1-O-benzyl-[5-O-benzoyl-β-D-apiofuranosyl (1→2)]-β-D-glucopyranoside (1), and 4`-hydroxy-7,3`-dimethoxyflavan-5-O- β-D-gluco-pyranoside (2), together with nine known flavanones 3 - 11, have been isolated from the dried whole plants of Viscum articulatum.Their structures were identified by extensive spectral analysis, especially 2D NMR techniques. Compound 9 showed weak anti-HIV-1 activity. Full article
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200 KiB  
Article
A Comparative Study of the Radical-scavenging Activity of the Phenolcarboxylic Acids Caffeic Acid, p-Coumaric Acid, Chlorogenic Acid and Ferulic Acid, With or Without 2-Mercaptoethanol, a Thiol, Using the Induction Period Method
by Yoshinori Kadoma and Seiichiro Fujisawa
Molecules 2008, 13(10), 2488-2499; https://doi.org/10.3390/molecules13102488 - 15 Oct 2008
Cited by 68 | Viewed by 18040
Abstract
Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione), a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME), as a [...] Read more.
Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione), a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME), as a substitute for GSH, was investigated by the induction period (IP) method for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radicals, R.) and benzoyl peroxide (BPO, a source of peroxy radicals, PhCOO.) using differential scanning calorimetry (DSC). Upon PhCOO. radical scavenging, the stoichiometric factors (n, number of free radical trapped by one mole of antioxidant) for caffeic acid, ferulic acid, p-coumaric acid and chlorogenic acid were 2.4, 1.8, 1.7 and 0.9, whereas upon R. radical scavenging, the corresponding values were 1.3, 1.2, 1.0 and 0.8, respectively. Antioxidants with n values close to 2 suggest the stepwise formation of semiquinone radicals and quinones. By contrast, those with n values close to 1 suggest the formation of dimers after single-electron oxidation, possibly due to recombination of corresponding aryloxy radicals. The ratio of the rate constant of inhibition to that of propagation (kinh/kp) declined in the order chlorogenic acid > p-coumaric acid > ferulic acid > caffeic acid. The ratio of the observed IP for the phenolcarboxylic acid/2-mercapto-ethanol (ME) mixture (1:1 molar ratio) (A) to the calculated IP (the simple sum of phenol acid antioxidant and ME) (B) was investigated. Upon R. scavenging, the caffeic acid or p-coumaric acid/ME mixture was A/B > 1, particularly the former was 1.2, suggesting a synergic effect. By contrast, upon PhCOO. scavenging, the corresponding mixture was A/B < 1, particularly the latter was 0.7, suggesting an antagonistic effect. Upon both radicals scavenging, the A/B for the ferulic acid or chlorogenic acid/ME mixture was approximately 1. The reported beneficial antioxidant, anti-inflammatory and anticancer effects of caffeic acid and p-coumaric acid may be related to their prooxidant-antioxidant balance in the presence of GSH. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
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345 KiB  
Article
Variation of Ursolic Acid Content in Eight Ocimum Species from Northeastern Brazil
by M. Goretti V. Silva, Icaro G. P. Vieira, Francisca N. P. Mendes, Irineu L. Albuquerque, Rogério N. Dos Santos, Fábio O. Silva and Selene M. Morais
Molecules 2008, 13(10), 2482-2487; https://doi.org/10.3390/molecules13102482 - 14 Oct 2008
Cited by 101 | Viewed by 18873
Abstract
Ursolic acid is a very important compound due to its biological potential as an anti-inflammatory, trypanocidal, antirheumatic, antiviral, antioxidant and antitumoral agent. This study presents the HPLC analysis of ursolic acid (UA) content in eight different Ocimum species: O. americanum L., O. basilicum [...] Read more.
Ursolic acid is a very important compound due to its biological potential as an anti-inflammatory, trypanocidal, antirheumatic, antiviral, antioxidant and antitumoral agent. This study presents the HPLC analysis of ursolic acid (UA) content in eight different Ocimum species: O. americanum L., O. basilicum L, O. basilicum var purpurascens Benth, O. basilicum var. minimum L, O. gratissimum L, O. micranthum Willd, O. selloi Benth. and O. tenuiflorum L. grown in Northeastern Brazil. In these Ocimum species, UA was detected in different yields, with O. tenuiflorum showing the highest content (2.02%). This yield is very significant when compared with other sources of UA. Full article
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243 KiB  
Article
Norcyperone, a Novel Skeleton Norsesquiterpene from Cyperus rotundus L.
by Yan Xu, Hong-Wu Zhang, Chang-Yuan Yu, Yang Lu, Ying Chang and Zhong-Mei Zou
Molecules 2008, 13(10), 2474-2481; https://doi.org/10.3390/molecules13102474 - 10 Oct 2008
Cited by 43 | Viewed by 12023
Abstract
A novel norsesquiterpene, named norcyperone (1), and three known compounds: (-)-clovane-2,9-diol (2), rosenonolactone (3), and 5a,8a-epidioxy-(20S,22E,24R)-ergosta-6,22-dien-3β-ol (4) were isolated from the rhizomes of Cyperus rotundus L. The structure of 1 was [...] Read more.
A novel norsesquiterpene, named norcyperone (1), and three known compounds: (-)-clovane-2,9-diol (2), rosenonolactone (3), and 5a,8a-epidioxy-(20S,22E,24R)-ergosta-6,22-dien-3β-ol (4) were isolated from the rhizomes of Cyperus rotundus L. The structure of 1 was elucidated as 8,11,11-trimethylbicyclo[5.3.1]undecane-5a, 8a-epoxy-3-one on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR, MS experiments, and single-crystal X-ray diffraction. This is the first report of a 8,11,11-trimethyl- bicyclo[5.3.1]undecane-3-one type norsesquiterpene with a tetrahydrofuran ring at C-5 and C-8. Full article
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203 KiB  
Article
Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)
by Vera Rosenkranz and Michael Wink
Molecules 2008, 13(10), 2462-2473; https://doi.org/10.3390/molecules13102462 - 3 Oct 2008
Cited by 73 | Viewed by 14927
Abstract
The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the [...] Read more.
The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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Article
Design and Synthesis of Bis-amide and Hydrazide-containing Derivatives of Malonic Acid as Potential HIV-1 Integrase Inhibitors
by Mario Sechi, Ugo Azzena, Maria Paola Delussu, Roberto Dallocchio, Alessandro Dessì, Alessia Cosseddu, Nicolino Pala and Nouri Neamati
Molecules 2008, 13(10), 2442-2461; https://doi.org/10.3390/molecules13102442 - 1 Oct 2008
Cited by 39 | Viewed by 17391
Abstract
HIV-1 integrase (IN) is an attractive and validated target for the development of novel therapeutics against AIDS. In the search for new IN inhibitors, we designed and synthesized three series of bis-amide and hydrazide-containing derivatives of malonic acid. We performed a docking study [...] Read more.
HIV-1 integrase (IN) is an attractive and validated target for the development of novel therapeutics against AIDS. In the search for new IN inhibitors, we designed and synthesized three series of bis-amide and hydrazide-containing derivatives of malonic acid. We performed a docking study to investigate the potential interactions of the title compounds with essential amino acids on the IN active site. Full article
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463 KiB  
Article
Discovery of a Novel CCR5 Antagonist Lead Compound Through Fragment Assembly
by Yanqing Liu, Enkun Zhou, Kunqian Yu, Jin Zhu, Yu Zhang, Xin Xie, Jian Li and Hualiang Jiang
Molecules 2008, 13(10), 2426-2441; https://doi.org/10.3390/molecules13102426 - 1 Oct 2008
Cited by 28 | Viewed by 14581
Abstract
CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4-yl)piperazin-1-yl)butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction [...] Read more.
CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4-yl)piperazin-1-yl)butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction with a calcium mobilization assay, a series of novel small molecule CCR5 antagonists have been designed and synthesized through fragment assembly. Preliminary SARs were obtained, which are in good agreement with the molecular binding model and should prove helpful for future antagonist design. The novel scaffold presented here might also be useful in the development of maraviroc-derived second generation CCR5 antagonists. Full article
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185 KiB  
Article
Characterization of Hydrocortisone Biometabolites and 18S rRNA Gene in Chlamydomonas reinhardtii Cultures
by Younes Ghasemi, Sara Rasoul-Amini, Mohammad Hossein Morowvat, Mohammad Javad Raee, Mohammad Bagher Ghoshoon, Fatemeh Nouri, Narges Negintaji, Rezvan Parvizi and Seyed Bagher Mosavi-Azam
Molecules 2008, 13(10), 2416-2425; https://doi.org/10.3390/molecules13102416 - 1 Oct 2008
Cited by 21 | Viewed by 14814
Abstract
A unicellular microalga, Chlamydomonas reinhardtii, was isolated from rice paddy-field soil and water samples and used in the biotransformation of hydrocortisone (1). This strain has not been previously tested for steroid bioconversion. Fermentation was carried out in BG-11 medium supplemented with 0.05% [...] Read more.
A unicellular microalga, Chlamydomonas reinhardtii, was isolated from rice paddy-field soil and water samples and used in the biotransformation of hydrocortisone (1). This strain has not been previously tested for steroid bioconversion. Fermentation was carried out in BG-11 medium supplemented with 0.05% substrate at 25ºC for 14 days of incubation. The products obtained were chromatographically purified and characterized using spectroscopic methods. 11b,17b-Dihydroxyandrost-4-en-3-one (2), 11b-hydroxyandrost-4-en-3,17-dione (3), 11b,17a,20b,21-tetrahydroxypregn-4-en-3-one (4) and prednisolone (5) were the main products of the bioconversion. The observed bioreaction features were the side chain degradation of the substrate to give compounds 2 and 3 and the 20-ketone reduction and 1,2-dehydrogenation affording compounds 4 and 5, respectively. A time course study showed the accumulation of product 2 from the second day of the fermentation and of compounds 3, 4 and 5 from the third day. All the metabolites reached their maximum concentration in seven days. Microalgal 18S rRNA gene was also amplified by PCR. PCR products were sequenced to confirm their authenticity as 18S rRNA gene of microalgae. The result of PCR blasted with other sequenced microalgae in NCBI showed 100% homology to the 18S small subunit rRNA of two Chlamydomonas reinhardtii spp. Full article
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298 KiB  
Article
Molecular Weight and Monosaccharide Composition of Astragalus Polysaccharides
by Du-Juan Xu, Quan Xia, Jia-Jia Wang and Pei-Pei Wang
Molecules 2008, 13(10), 2408-2415; https://doi.org/10.3390/molecules13102408 - 1 Oct 2008
Cited by 57 | Viewed by 15414
Abstract
Two polysaccharides (APS-I and APS-II) were isolated from the water extract of Radix Astragali and purified through ethanol precipitation, deproteination and by ion-exchange and gel-filtration chromatography. Their molecular weight was determined using high performance liquid chromatography and gel permeation chromatography (HPLC-GPC) and their [...] Read more.
Two polysaccharides (APS-I and APS-II) were isolated from the water extract of Radix Astragali and purified through ethanol precipitation, deproteination and by ion-exchange and gel-filtration chromatography. Their molecular weight was determined using high performance liquid chromatography and gel permeation chromatography (HPLC-GPC) and their monosaccharide composition was analyzed by TLC and HPLC methods, using a refractive index detector (RID) and an NH2 column. It was shown that APS-I consisted of arabinose and glucose and APS-II consisted of rhamnose, arabinose and glucose, in a molar ratio of 1:3.45 and 1:6.25:17.86, respectively. The molecular weights (Mw) of APS-I and APS-II were 1,699,100 Da and 1,197,600 Da, respectively. Full article
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219 KiB  
Article
Methyl Mercapturate Synthesis: An Efficient, Convenient and Simple Method
by Benoît Cossec, Frédéric Cosnier and Manuella Burgart
Molecules 2008, 13(10), 2394-2407; https://doi.org/10.3390/molecules13102394 - 1 Oct 2008
Cited by 11 | Viewed by 11745
Abstract
A safe and simple method for methyl S-arylmercapturate synthesis is described. Thirteen such compounds, to be used afterwards in metabolism studies, have been obtained with yields ranging from 71 to 99.6%. These compounds were obtained using a sulfa-Michael addition and synthesized by adding [...] Read more.
A safe and simple method for methyl S-arylmercapturate synthesis is described. Thirteen such compounds, to be used afterwards in metabolism studies, have been obtained with yields ranging from 71 to 99.6%. These compounds were obtained using a sulfa-Michael addition and synthesized by adding the corresponding thiophenols to a mixture composed of methyl 2-acetamidoacrylate (MAA), potassium carbonate and a phase transfer catalyst, Aliquat 336. MAA, the initial synthon, was itself isolated in quasi quantitative yield following a fully described synthesis. Full article
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194 KiB  
Article
Antibacterial Properties of 3 H-Spiro[1-benzofuran-2,1’-cyclohexane] Derivatives from Heliotropium filifolium
by Alejandro Urzúa, Javier Echeverría, Marcos C. Rezende and Marcela Wilkens
Molecules 2008, 13(10), 2385-2393; https://doi.org/10.3390/molecules13102385 - 1 Oct 2008
Cited by 39 | Viewed by 10374
Abstract
A re-examination of cuticular components of Heliotropium filifolium allowed the isolation of four new compounds: 3’-hydroxy-2’,2’,6’-trimethyl-3H-spiro[1-benzo-furan-2,1’-cyclohexane]-5-carboxylic acid(2), methyl 3’-acetyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (3), methyl 3’-isopentanoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (4) and methyl 3’-benzoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their spectroscopic analogies with [...] Read more.
A re-examination of cuticular components of Heliotropium filifolium allowed the isolation of four new compounds: 3’-hydroxy-2’,2’,6’-trimethyl-3H-spiro[1-benzo-furan-2,1’-cyclohexane]-5-carboxylic acid(2), methyl 3’-acetyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (3), methyl 3’-isopentanoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (4) and methyl 3’-benzoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their spectroscopic analogies with filifolinol (1), and their structures confirmed by chemical correlation with 1. The antimicrobial properties of the compounds were tested against Gram positive and Gram negative bacteria. Some of them proved to be active against Gram positive, but inactive against Gram negative bacteria. In searching for structure-activity relationships from the obtained MIC values, lipophilicity was shown to be an important variable. Full article
(This article belongs to the Special Issue Spiro Compounds)
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248 KiB  
Review
Radiation- and Photo-induced Activation of 5-Fluorouracil Prodrugs as a Strategy for the Selective Treatment of Solid Tumors
by Takeo Ito, Kazuhito Tanabe, Hisatsugu Yamada, Hiroshi Hatta and Sei-ichi Nishimoto
Molecules 2008, 13(10), 2370-2384; https://doi.org/10.3390/molecules13102370 - 1 Oct 2008
Cited by 30 | Viewed by 14556
Abstract
5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that [...] Read more.
5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation. Full article
(This article belongs to the Special Issue 5-Fluorouracil)
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717 KiB  
Review
Novel Strategies to Improve the Anticancer Action of 5-Fluorouracil by Using Drug Delivery Systems
by José L. Arias
Molecules 2008, 13(10), 2340-2369; https://doi.org/10.3390/molecules13102340 - 1 Oct 2008
Cited by 197 | Viewed by 16817
Abstract
Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of the anticancer drug 5-fluorouracil have been devised. The target is always to provide the proper dose of [...] Read more.
Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of the anticancer drug 5-fluorouracil have been devised. The target is always to provide the proper dose of the antitumor agent only at the desired locus of action, thus reducing the unwanted side effects. In this review, the main strategies and the more significant results in the development of 5-fluorouracil carriers for cancer treatment are discussed. Full article
(This article belongs to the Special Issue 5-Fluorouracil)
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