Production of biologically active oxidized derivatives of finasteride through metabolism by Aspergillus niger culture.

CONTEXT: Among the 4-azasteroids, finasteride is biologically the most important compound having preventive effect against male pattern baldness (MPH) and benign prostatic hyperplasia commonly called enlargement of prostate gland. OBJECTIVE: The microbial transformation of finasteride by fungus Aspergillus niger (ATCC 10549) has been investigated to obtain biologically more potent derivatives. MATERIALS AND METHODS: Fermentation of finasteride was performed with filamentous fungus Aspergillus niger (ATCC 10549). This transformation resulted in the production of two transformed products, which were purified through column chromatography. In vitro lipoxygenase inhibitory potential was determined by incubating 20 mL of the enzyme with 10 mL of test sample (100 µM) in 0.1 mM (pH 7.0) phosphate buffer for 5 min at 258 °C followed by addition of 10 µL of substrate (linolenic acid) to reaction mixture and measuring the formation of complex spectrophotometrically. RESULTS: Structure elucidation of biotransformed metabolites was ascertained through extensive 1D and 2D spectroscopic techniques. This study established the fact that A. niger promoted stereospecific dihydroxylation at C-11 and C-15 of finasteride. The resulting biotransformed metabolites were characterized as 11α-hydroxyfinasteride and 15ß-hydroxyfinasteride, respectively. Finasteride along with transformed metabolites were analyzed for their in vitro lipoxygenase (LOX) inhibition assay. Among the tested compounds 15ß-hydroxyfinasteride showed good activity with IC50 value 112.56 ± 2.23 µM while inhibitory effect in case of 11α-hydroxyfinasteride was low with IC50 value 186.05 ± 1.34 µM. Standard compound baicalein revealed IC50 value being 22.0 ± 0.05 µM. CONCLUSION: The present investigation highlighted the fact that potentially active compound can be produced through the technology of biotransformation.