Microbial transformation of epothilone A by Aspergillus niger AS 3.739

Abstract

The microbiological transformation of epothilone A (1) by Aspergillus niger AS 3.739 afforded four main metabolites. Their structures were elucidated by ¹H, ¹³C NMR and HSQC, COSY, HMBC, and NOESY spectra as trans-12,13-hydroxylated epothilone A (2), cis-12,13-hydroxylated epothilone A (3), trans-12,15-epoxidated epothilone A (4), and cis-12,15-epoxidated epothilone A (5). All four compounds were firstly found based on their stereochemistry. These new compounds displayed cytotoxicity against human breast carcinoma cells MCF-7 with IC₅₀ 9.88 μg/ml of 2, 2.52 μg/ml of 3, 9.88 μg/ml of 4, and 5.68 μg/ml of 5.

Keywords:

• epothilone A
• microbial transformation
• Aspergillus niger
• cytotoxicity

Acknowledgement

We wish to thank the NMR Laboratory, National Center of Biomedical Analysis for suggestions and preparation of NMR spectrum.