Biotransformation of oral contraceptive ethynodiol diacetate with microbial and plant cell cultures

Abstract

BackgroundBiotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (1) by using plant and microbial cultures.ResultsThe biotransformation of ethynodiol diacetate (1) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3β,17β-diacetoxy-6α-ol (2), 17α-ethynylestr-4-en-3β,17β-diacetoxy-6β-ol (3), and 17α-ethynylestr-4-en-3β,17β-diacetoxy-10β-ol (4) and a known metabolite, 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5). The biotransformation of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5), 17α-ethynyl-17β-hydroxyestr-4-en-3-one (6), 17α-ethynyl-3 β-hydroxy-17β-acetoxyestr-4-ene (7) and 17α-ethynyl-5α,17β-dihydroxyestr-3-ene (8). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6. Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies.ConclusionBiotransformation of an oral contraceptive, ethynodiol diacetate (1), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.

In-vitro immunomodulatory and anti-cancerous activities of biotransformed products of Dianabol through Azadirachta indica and its molecular docking studies

“…Plant biotransformation of various steroids has already been described by many groups in which different reactions were observed for instances a report explains the changes in ethynodiol diacetate by the suspension culture of Ocimum basilicum and the same plant, in this article biotransformation with Ocimum basilicum performed hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group and with A indica hydrolysis of the ester group, oxidation/reduction reactions were observed [14]. Similarly, biotransformation of 21-O-acetyl-deoxycorticosterone by cell suspension cultures of Digitalis lanata illustrates how plant cell suspension can carry out unique reactions; 2β-Hydroxylation and C-21-glucosylation of the steroidal nucleus was being reported first time by plant-culture cells besides 5α and 5β reduction [17].…”

Efficient Protocol for In vitro Regeneration of Ocimum sanctum using Nodal Segments as Explants

“…There are previous reports available on O. sanctum invitro propagation using other explants sources, but this is the first report of in-vitro multiplication using nodal segments as explants. The main rationale of this study was to develop a sterile germ-plasm source that can be used for other in-vitro studies like bio-transformation (Zafar et al, 2012) and protoplast manipulations.…”

Transferred multipolar atom model for 10β,17β-dihydroxy-17α-methylestr-4-en-3-one dihydrate obtained from the biotransformation of methyloestrenolone

“…Biotransformation or biocatalysis is the structural modification of compounds using enzymes as the catalysts (Mahato & Garai, 1997). Biotransformation using whole-cell cultures of microorganisms is an efficient method for the production of libraries of structurally diverse molecules, starting from a single substrate (Mahato & Garai, 1997;Ahmad et al, 2014;Khan et al, 2014;Zafar et al, 2012;Leon et al, 1998;Holland, 1999). This methodology has been applied to the synthesis of bioactive molecules of varying nature (Choudhary et al, 2012;Monagas et al, 2010;Liu & Yu, 2010;Cao et al, 2015;Wang, 2015).…”