ABSTRACT
The fungal transformation of cedryl acetate (1) was investigated for the first time by using Cunninghamella elegans. The metabolites obtained include, 10ß-hydroxycedryl acetate (3), 2α, 10ß-dihydroxycedryl acetate (4), 2α-hydroxy-10-oxocedryl acetate (5), 3α,10ß-dihydroxycedryl acetate (6), 3α,10α-dihydroxycedryl acetate (7), 10ß,14α-dihydroxy cedryl acetate (8), 3ß,10ß-cedr-8(15)-ene-3,10-diol (9), and 3α,8ß,10ß -dihydroxycedrol (10). Compounds 1, 2, and 4 showed α-glucosidase inhibitory activity, whereby 1 was more potent than the standard inhibitor, acarbose, against yeast α-glucosidase. Detailed docking studies were performed on all experimentally active compounds to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homolog, the intestinal maltase, by an average value of approximately -1.4 kcal/mol, however, no significant difference was observed in the case of pancreatic amylase.
Subject(s)
Acetates/metabolism , Acetates/pharmacology , Cunninghamella/chemistry , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors , Quantum Theory , Sesquiterpenes/metabolism , Sesquiterpenes/pharmacology , Acetates/chemistry , Cunninghamella/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Humans , Intestinal Mucosa/metabolism , Intestines/enzymology , Models, Molecular , Molecular Conformation , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/metabolism , Sesquiterpenes/chemistry , Stereoisomerism , Structure-Activity Relationship , alpha-Glucosidases/metabolismABSTRACT
The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and 6beta,12beta-dihydroxymestranol (3). Metabolite 3 was found to be a new compound. These metabolites were structurally characterized on the basis of spectroscopic techniques.
