Biocatalytic modifications of ethynodiol diacetate by fungi, anti-proliferative activity, and acetylcholineterase inhibitory of its transformed products

Nurfazilah Wan Yusop S 1 , Imran S 2 , Ilham Adenan M 3 , Ashraf K 1 , Sultan S 4

Affiliations 

  • 1 Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, 42300 Kuala Selangor, Selangor, Malaysia; Atta-ur-Rahman Institute for Natural Product Discovery (AuRins), Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, 42300 Kuala Selangor, Selangor, Malaysia
  • 2 Atta-ur-Rahman Institute for Natural Product Discovery (AuRins), Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, 42300 Kuala Selangor, Selangor, Malaysia; Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450 Shah Alam, Selangor, Malaysia
  • 3 Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450 Shah Alam, Selangor, Malaysia; Universiti Teknologi MARA, Pahang Branch, Bandar Tun Abdul Razak, 26400 Jengka, Pahang, Malaysia
  • 4 Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, 42300 Kuala Selangor, Selangor, Malaysia; Atta-ur-Rahman Institute for Natural Product Discovery (AuRins), Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, 42300 Kuala Selangor, Selangor, Malaysia. Electronic address: drsadia@uitm.edu.my
Steroids, 2021 Jul;171:108832.
PMID: 33831403 DOI: 10.1016/j.steroids.2021.108832

Abstract

The fungal transformations of ethynodiol diacetate (1) were investigated for the first-time using Botrytis cinerea, Trichothecium roseum, and R3-2 SP 17. The metabolites obtained are as following: 17α-Ethynyl-17β-acetoxyestr-4-en-3-one-15β-ol (2), 19-nor-17a-ethynyltestosterone (3), and 17α-ethynyl-3β-hydroxy-17β-acetoxyestr-4-ene (4). The new metabolite, 2 (IC50 = 104.8 µM), which has ketone group at C-3, and the β-hydroxyl group at C-15, resulted in an almost equipotent strength with the parent compound (IC50 = 103.3 µM) against proliferation of SH-SY5Y cells. The previously reported biotransformed product, 3, showed almost equal strength to 1 against acetylcholinesterase. Molecular modelling studies were carried out to understand the observed experimental activities, and also to obtain more information on the binding mode and the interactions between the biotransformed products, and enzyme.

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