Biotransformation of finasteride by Ocimum sanctum L., and tyrosinase inhibitory activity of transformed metabolites: experimental and computational insights

Sajid Ali; Muhammad Nisar; Marcello Iriti; Mohammad Raza Shah; Maqsood Mahmud; Ihsan Ali; Inamullah Khan

doi:10.1016/j.steroids.2014.07.007

Biotransformation of finasteride by Ocimum sanctum L., and tyrosinase inhibitory activity of transformed metabolites: experimental and computational insights

Steroids. 2014 Dec:92:20-4. doi: 10.1016/j.steroids.2014.07.007. Epub 2014 Aug 23.

Authors

Sajid Ali¹, Muhammad Nisar², Marcello Iriti³, Mohammad Raza Shah⁴, Maqsood Mahmud⁵, Ihsan Ali¹, Inamullah Khan⁶

Affiliations

¹ Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan.
² Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan. Electronic address: akhund54@gmail.com.
³ Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy. Electronic address: marcello.iriti@unimi.it.
⁴ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁵ Department of Information Systems, College of Computer and Information Sciences (CCIS), King Saud University, Saudi Arabia.
⁶ Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan.

PMID: 25159102
DOI: 10.1016/j.steroids.2014.07.007

Abstract

Transformation of Finasteride (I) by cell suspension cultures of Ocimum sanctum L. was investigated. Fermentation of compound (I) with O. sanctum afforded three oxidized derivatives, 16β-hydroxyfinasteride (II), 11α-hydroxyfinasteride (III) and 15β-hydroxyfinasteride (IV). Among these metabolites, compound (II) was a new metabolite. Compound (I) and its derivatives were studied for their tyrosinase inhibition assay. All test compounds exhibited significant activity compared to standard drug kojic acid, with compound IV being the most potent member with an IC50 of 1.87μM. Molecular docking revealed significant molecular interactions behind the potent tyrosinase inhibitory activity of the tested compounds.

Keywords: 11α-Hydroxyfinasteride; 15β-Hydroxyfinasteride; 16β-Hydroxyfinasteride; Finasteride; Ocimum sanctum L.; Tyrosinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / metabolism*
Enzyme Inhibitors / pharmacology*
Finasteride / metabolism*
Finasteride / pharmacology*
Monophenol Monooxygenase / antagonists & inhibitors*
Ocimum / metabolism*

Substances

Enzyme Inhibitors
Finasteride
Monophenol Monooxygenase