Microbial metabolism of methyl protodioscin by Aspergillus niger culture--a new androstenedione producing way from steroid.
Methyl protodioscin (1), a natural furostanol biglycoside steroid, was a preclinical anticancer drug, which showed potent activity against most cell lines from leukemia and solid tumors in the National Cancer Institute's (NCI) human cancer panel. Metabolism of methyl protodioscin by Aspergillus niger was investigated. Seven metabolites were isolated and identified. Two main metabolites were pregnane glycosides and four were furostanol glycosides, together with the aglycone. It was found that steroidal saponin skeleton could be converted to pregnenolone skeleton only using microbial methods, which must have chemical procedures in the reported literatures. The proposed biosynthetic pathways of the microbial conversion products of methyl protodioscin were drawn. The found enriched the reaction types of microbial bioconversion and provided a new producing way of androstenedione from steroid. Most metabolites showed strong cytotoxic activities against HepG2, NCI-H460, HeLa, and MCF-7 cell lines.
He
Xiangjiu
X
Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China. xh35@cornell.edu
Liu
Bo
B
Wang
Guanghui
G
Wang
Xinluan
X
Su
Lina
L
Qu
Gexia
G
Yao
Xinsheng
X
D000230:Adenocarcinoma / Q000188:drug therapy; D000735:Androstenedione / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001234:Aspergillus niger / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D012503:Saponins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013256:Steroids / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D012503:Saponins; D013256:Steroids; C425324:methyl protodioscin; D000735:Androstenedione; D004144:Diosgenin