Microbial transformations of the antimelanoma agent betulinic acid.
Microbial transformation studies of the antimelanoma agent betulinic acid (1) were conducted. Screening experiments showed a number of microorganisms capable of biotransforming 1. Three of these cultures, Bacillus megaterium ATCC 14581, Cunninghamella elegans ATCC 9244, and Mucor mucedo UI-4605, were selected for preparative scale transformation. Bioconversion of 1 with resting-cell suspensions of phenobarbital-induced B. megaterium ATCC 14581 resulted in the production of the known betulonic acid (2) and two new metabolites: 3beta,7beta-dihydroxy-lup-20(29)-en-28-oic acid (3) and 3beta,6alpha, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (4). Biotransformation of 1 with growing cultures of C. elegans ATCC 9244 produced one new metabolite characterized as 1beta,3beta, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (5). Incubation of 1 with growing cultures of M. mucedo UI-4605 afforded metabolite 3. Structure elucidation of all metabolites was based on NMR and HRMS analyses. In addition, the antimelanoma activity of metabolites 2-5 was evaluated against two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).
Kouzi
S A
SA
Department of Pharmaceutics and Medicinal Chemistry, School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA. skouzi@uop.edu
Chatterjee
P
P
Pezzuto
J M
JM
Hamann
M T
MT
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001410:Bacillus megaterium / Q000378:metabolism*; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy*; D053978:Pentacyclic Triterpenes; D013057:Spectrum Analysis; D014315:Triterpenes / Q000378:metabolism*; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid