title: Production of a highly potent epoxide through the microbial metabolism of 3β-acetoxyurs-11-en-13β,28-olide by Aspergillus niger culture.
abstract: Context 3β-Acetoxyurs-11-en-13β,28-olide (I), a triterpenoid, is found in most plant species. Pharmacologically triterpenes are very effective compounds with potent anticancer, anti-HIV and antimicrobial activities. Objectives Microbial transformation of 3β-acetoxyurs-11-en-13β,28-olide (I) was performed in order to obtain derivatives with improved pharmacological potential. Materials and methods Compound (I, 100 mg) was incubated with Aspergillus niger culture for 12 d. The metabolite formed was purified through column chromatography. Structure elucidation was performed through extensive spectroscopy (IR, MS and NMR). In vitro α- and β-glucosidase inhibitory, and antiglycation potentials of both substrate and metabolite were evaluated. Results Structure of metabolite II was characterized as 3β-acetoxyurs-11,12-epoxy-13β,28-olide (II). Metabolite II was found to be an oxidized product of compound I. In vitro α- and β-glucosidases revealed that metabolite II was a potent and selective inhibitor of α-glucosidase (IC50 value = 3.56 ± 0.38 μM), showing that the inhibitory effect of metabolite II was far better than compound I (IC50 value = 14.7 ± 1.3 μM) as well as acarbose (IC50 value = 545 ± 7.9 μM). Antiglycation potential of compound II was also high with 82.51 ± 1.2% inhibition. Thus, through oxidation, the biological potential of the substrate molecule can be enhanced. Conclusion Biotransformation can be used as a potential tool for the production of biologically potent molecules.
authors.affiliation: a Department of Chemistry , Bacha Khan University , Charsadda , Pakistan ;
authors.forename: Sajid
authors.initials: S
authors.lastname: Ali
authors.affiliation: b Institute of Chemical Sciences, University of Peshawar , Peshawar , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Nisar
authors.affiliation: a Department of Chemistry , Bacha Khan University , Charsadda , Pakistan ;
authors.forename: Hussain
authors.initials: H
authors.lastname: Gulab
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D001234:Aspergillus niger / Q000378:metabolism*; D001711:Biotransformation; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017127:Glycation End Products, Advanced; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism*; D000093423:Glycated Serum Albumin
chemical_list: C000614081:3-acetoxy-11,12-epoxyurs-13,28-olide; D004852:Epoxy Compounds; D017127:Glycation End Products, Advanced; D065089:Glycoside Hydrolase Inhibitors; D012709:Serum Albumin; D014315:Triterpenes; D012710:Serum Albumin, Bovine; D020909:Acarbose; D000093423:Glycated Serum Albumin
keywords: Acarbose; antiglycation; metabolite; spectroscopy; α-glucosidase