ABSTRACT
A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
Subject(s)
Amides/pharmacology , Antineoplastic Agents/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , bcl-X Protein/antagonists & inhibitors , Amides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Line, Tumor , Cyclohexanecarboxylic Acids/chemical synthesis , Drug Screening Assays, Antitumor , Humans , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/pharmacology , StereoisomerismABSTRACT
An alkaloidal extract of the leaves of Melochia odorata exhibited antifungal activity against Candida albicans, Cryptococcus neoformans and Saccharomyces cerevisiae using a TLC bioautographic method. Bioassay-guided fractionation of this extract using separation by normal and reverse high-performance liquid chromatography (HPLC) resulted in the isolation of two active compounds identified as frangulanine, a cyclic peptide alkaloid, and waltherione-A, a quinolinone alkaloid.
Subject(s)
Alkaloids/isolation & purification , Antifungal Agents/isolation & purification , Malvaceae/chemistry , Alkaloids/pharmacology , Antifungal Agents/pharmacology , Candida albicans/drug effects , Cryptococcus neoformans/drug effects , Microbial Sensitivity Tests , Plant Leaves/chemistry , Saccharomyces cerevisiae/drug effectsABSTRACT
This study examined the vascular effect of Arbutus leaves (aqueous extract) and described the isolation of several fractions responsible for their vasorelaxant activity. The aqueous extract (AE) of leaves was tested on rat aortic rings precontracted with 0.1 microm noradrenaline. At 10(-2) g/L, AE produced an endothelium dependent relaxation of 66% +/- 5%, (n = 8). The leaves of Arbutus were then extracted successively with different solvents and the methanol extract was the most active. When tannins (primarily condensed tannins) were precipitated from the methanol extract, they showed a strong vasorelaxant activity (87% +/- 4%, n = 5), whereas the elimination of tannins in the methanol extract reduced significantly its vasorelaxant activity (42% +/- 8%, n = 8, p < 0.005). The methanol extract was further separated semi-preparatively by reversed-phase HPLC. Four fractions (Fr2, Fr3, Fr4 and Fr6) were the most active and produced 88% +/- 2% (n = 5), 75% +/- 6% (n = 5), 76% +/- 3% (n = 7) and 77% +/- 3% (n = 10) relaxation, respectively. These four fractions mainly correspond to polyphenol compounds. Analysis of Fr6 indicated that this fraction contained catechin gallate. In conclusion, the vasorelaxant activity of Arbutus is likely to be due to polyphenol compounds, primarily condensed tannins and catechin gallate.
Subject(s)
Aorta, Thoracic/drug effects , Catechin/analogs & derivatives , Endothelium, Vascular/drug effects , Ericaceae , Phytotherapy , Plant Extracts/pharmacology , Vasodilator Agents/pharmacology , Animals , Catechin/administration & dosage , Catechin/pharmacology , Catechin/therapeutic use , Male , Norepinephrine , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves , Rats , Rats, Wistar , Tannins/administration & dosage , Tannins/pharmacology , Tannins/therapeutic use , Vasodilator Agents/administration & dosage , Vasodilator Agents/therapeutic useABSTRACT
An alkaloidal extract of the stem barks of Zanthoxylum chiloperone var. angustifolium exhibited antifungal activity against Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes var. interdigitale using a TLC bioautographic method. Bioassay-guided fractionation of this extract resulted in the isolation of two active compounds identi fi ed as canthin-6-one and 5-methoxycanthin-6-one. Canthin-6-one exhibited a broad spectrum of activities against Aspergillus fumigatus, A. niger, A. terreus, Candida albicans, C. tropicalis, C. glabrata, Cryptococcus neoformans, Geotrichum candidum, Saccharomyces cerevisiae, Trichosporon beigelii, Trichosporon cutaneum and Trichophyton mentagrophytes var. interdigitale with MICs values between 5.3 and 46 micro mol/L. 5-methoxy-canthin-6-one was active against only Trichophyton mentagrophytes var. interdigitale with a MIC value of 12.3 micro mol/L.