Microbial transformation of 14-deoxy-11, 12-didehydroandrographolide and 14-deoxyandrographolide and inhibitory effects on nitric oxide production of the transformation products

Microbial transformations of 14-deoxy-11, 12-didehydroandrographolide (a) and 14-deoxyandrographolide (b) were performed by Cunninghamella blakesleana (AS 3.970), respectively. Sixteen metabolites were obtained and their structures were elucidated by spectroscopic data analyses. Among these metabolites, 3α, 12S, 19-trihydroxy-8(17), 9(11)-ent-labdadien-16, 15-olide (a7), 3-oxo-8α, 17β-epoxy-14-deoxyandrographolide (b2), 3α, 17, 19-trihydroxy-8, 13-ent-labdadien-16, 15-olide (b6), and 9β-hydroxy-14-deoxyandrographolide (b9) are new compounds. The configuration of C-12 in metabolite a7 was determined as S by GIAO method. The proposed metabolic pathways of 14-deoxy-11, 12-didehydroandrographolide and 14-deoxyandrographolide by C. blakesleana were drawn. The inhibitory effects of these compounds on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated and their preliminary structure-activity relationships (SAR) were discussed.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Microbial transformation of 14-deoxy-11, 12-didehydroandrographolide gives seven metabolites. ► Microbial transformation of 14-deoxyandrographolide gives nine metabolites. ► Four metabolites are new compounds. ► Some metabolites show inhibitory effects on nitric oxide production. ► Structure-activity relationships are discussed.