Molecules

323 KiB

Open AccessArticle

HPLC-ESI-MS/MS of Imidazole Alkaloids in Pilocarpus microphyllus

by Alexandra Sawaya, Ilka Nacif Abreu, Nathalia Luiza Andreazza, Marcos N. Eberlin and Paulo Mazzafera

Molecules 2008, 13(7), 1518-1529; https://doi.org/10.3390/molecules13071518 - 30 Jul 2008

Cited by 20 | Viewed by 15360

Abstract

Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose [...] Read more.

Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose biosynthetic pathways are under investigation. In the present study, a HPLC method coupled with ESI-MSⁿ was developed for their qualitative and quantitative analysis. This method permits the chromatographic separation of the imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis of the individual compounds. Thus two samples: leaves of P. microphyllus and a paste that is left over after the industrial extraction of pilocarpine; were compared. The paste was found to contain significant amounts of pilocarpine and other imidazole alkaloids, but had a slightly different alkaloid profile than the leaf extract. The method is suitable for the routine analysis of samples containing these alkaloids, as well as for the separation and identification of known and novel alkaloids from this family, and may be applied to further studies of the biosynthetic pathway of pilocarpine in P. microphyllus. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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335 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of Some New Pyrazole, Fused Pyrazolo[3,4-d]-pyrimidine and Pyrazolo[4,3-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives

by Nada M. Abunada, Hamdi M. Hassaneen, Nadia G. Kandile and Omar A. Miqdad

Molecules 2008, 13(7), 1501-1517; https://doi.org/10.3390/molecules13071501 - 29 Jul 2008

Cited by 104 | Viewed by 12975

Abstract

Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- [...] Read more.

Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile) to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3H)one and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16a,b and 17a,b. Reactions of compounds 17a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19a,b, respectively. Full article

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280 KiB

Open AccessArticle

Synthesis and Antiproliferative Activities of 5-Azacytidine Analogues in Human Leukemia Cells

by Gang Guo, Gang Li, Dan Liu, Qian-Jiao Yang, Yu Liu, Yong-Kui Jing and Lin-Xiang Zhao

Molecules 2008, 13(7), 1487-1500; https://doi.org/10.3390/molecules13071487 - 23 Jul 2008

Cited by 6 | Viewed by 10288

Abstract

Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability [...] Read more.

Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells. Full article

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301 KiB

Open AccessArticle

Facile Synthesis of Oleanolic Acid Monoglycosides and Diglycosides

by Yu Sha, Mao-Cai Yan, Jiao Liu, Yang Liu and Mao-Sheng Cheng

Molecules 2008, 13(7), 1472-1486; https://doi.org/10.3390/molecules13071472 - 22 Jul 2008

Cited by 25 | Viewed by 12023

Abstract

Oleanolic acid and its glycosides are important natural products, possessing various attractive biological activities such as antitumor, antivirus and anti-inflammatory properties. In the present work, fifteen oleanolic acid saponins bearing various saccharide moieties, including 3-monoglycoside, 28-monoglycoside and 3,28-diglycoside, were easily synthesized in high [...] Read more.

Oleanolic acid and its glycosides are important natural products, possessing various attractive biological activities such as antitumor, antivirus and anti-inflammatory properties. In the present work, fifteen oleanolic acid saponins bearing various saccharide moieties, including 3-monoglycoside, 28-monoglycoside and 3,28-diglycoside, were easily synthesized in high yields. Benzyl was chosen as the protective group for the COOH(28) group, instead of commonly used methyl and allyl, to avoid difficulties in the final deprotection. Alkali-promoted condensation of the carboxylic acid with bromoglycosides was found to be more efficient in the synthesis of 28-glycosides. Two approaches were investigated and proved practicable in the preparation of 3,28- diglycosides. This method is suitable for preparing oleanolic acid glycosides with structural diversity for extensive biological evaluation and structure-activity relationship study, and it also apply new idea for the corresponding synthetic methods to the glycoside derivatives of other triterpenoid. Full article

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205 KiB

Open AccessArticle

Simplexidine, a 4-Alkylpyridinium Alkaloid from the Caribbean Sponge Plakortis simplex

by Ernesto Fattorusso, Adriana Romano, Fernando Scala and Orazio Taglialatela-Scafati

Molecules 2008, 13(7), 1465-1471; https://doi.org/10.3390/molecules13071465 - 17 Jul 2008

Cited by 7 | Viewed by 9436

Abstract

Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule, [...] Read more.

Chemical analysis of the secondary metabolites of the Caribbean sponge Plakortis simplex, a source of many bioactive compounds, showed the presence of the new metabolite simplexidine (4), belonging to the extremely rare class of 4-alkyl-pyridinium alkaloids. The structural characterization of this molecule, based on spectroscopic methods, is reported. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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293 KiB

Open AccessArticle

Phenolic Compounds in Field Horsetail (Equisetum arvense L.) as Natural Antioxidants

by Neda Mimica-Dukic, Natasa Simin, Jelena Cvejic, Emilija Jovin, Dejan Orcic and Biljana Bozin

Molecules 2008, 13(7), 1455-1464; https://doi.org/10.3390/molecules13071455 - 17 Jul 2008

Cited by 92 | Viewed by 21424

Abstract

In this paper, the study of antioxidant activity and phenolic composition of three different extracts (EtOAc, n-BuOH and H₂O) of field horsetail (Equisetum arvense L.) is presented. The antioxidant activity has been evaluated measuring the total reducing power (expressed by Ascorbate [...] Read more.

In this paper, the study of antioxidant activity and phenolic composition of three different extracts (EtOAc, n-BuOH and H₂O) of field horsetail (Equisetum arvense L.) is presented. The antioxidant activity has been evaluated measuring the total reducing power (expressed by Ascorbate Equivalent Antioxidant Capacity - AEAC), inhibition of lipid peroxidation, and free radical scavenging capacity (RSC) towards 2,2-diphenyl-1- picrylhydrazyl (DPPH radical) and nitric oxide (NO), respectively. In addition, the total flavonoid content (TFC) and phenolic constituents of each extract have been determined. The results obtained show that the highest RSC regarding both DPPH and NO radicals is expressed by EtOAc extract (EC₅₀=2.37 μg/mL and EC₅₀=90.07 μg/mL, respectively), and the lowest by H₂O extract (EC₅₀=37.2 μg/mL and EC₅₀>333.33 μg/mL, respectively). n- BuOH extract showed the highest total reducing power (AEAC=13.40 μg/mL). Differences in the phenolic composition of examined extracts are found comparing the HPLC chemical profiles. Although, isoquercitrin is the main flavonoid in both EtOAc and n-BuOH extracts, a considerable amount of di-E-caffeoyl-meso-tartaric acid was presented in the n-BuOH extract. In H₂O extract high content of phenolic acids and low percentage of flavonoids were detected. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics)

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199 KiB

Open AccessArticle

Enhanced Absorption and Growth Inhibition with Amino Acid Monoester Prodrugs of Floxuridine by Targeting hPEPT1 Transporters

by Yasuhiro Tsume, Balvinder S. Vig, Jing Sun, Christopher P. Landowski, John M. Hilfinger, Chandrasekharan Ramachandran and Gordon L. Amidon

Molecules 2008, 13(7), 1441-1454; https://doi.org/10.3390/molecules13071441 - 28 Jun 2008

Cited by 38 | Viewed by 11414

Abstract

A series of amino acid monoester prodrugs of floxuridine was synthesized and evaluated for the improvement of oral bioavailability and the feasibility of target drug delivery via oligopeptide transporters. All floxuridine 5′-amino acid monoester prodrugs exhibited PEPT1 affinity, with inhibition coefficients of Gly-Sar [...] Read more.

A series of amino acid monoester prodrugs of floxuridine was synthesized and evaluated for the improvement of oral bioavailability and the feasibility of target drug delivery via oligopeptide transporters. All floxuridine 5′-amino acid monoester prodrugs exhibited PEPT1 affinity, with inhibition coefficients of Gly-Sar uptake (IC50) ranging from 0.7 – 2.3 mM in Caco-2 and 2.0 – 4.8 mM in AsPC-1 cells, while that of floxuridine was 7.3 mM and 6.3 mM, respectively. Caco-2 membrane permeabilities of floxuridine prodrugs (1.01 – 5.31 x 10^-6cm/sec) and floxuridine (0.48 x 10^-6cm/sec) were much higher than that of 5-FU (0.038 x 10^-6 cm/sec). MDCK cells stably transfected with the human oligopeptide transporter PEPT1 (MDCK/hPEPT1) exhibited enhanced cell growth inhibition in the presence of the prodrugs. This prodrug strategy offers great potential, not only for increased drug absorption but also for improved tumor selectivity and drug efficacy. Full article

(This article belongs to the Special Issue 5-Fluorouracil)

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Molecules, Volume 13, Issue 7 (July 2008) – 7 articles , Pages 1441-1529

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