2. Academic Validation
  3. Medroxyprogesterone derivatives from microbial transformation as anti-proliferative agents and acetylcholineterase inhibitors (combined in vitro and in silico approaches)

Medroxyprogesterone derivatives from microbial transformation as anti-proliferative agents and acetylcholineterase inhibitors (combined in vitro and in silico approaches)

  • Steroids. 2020 Dec:164:108735. doi: 10.1016/j.steroids.2020.108735.
Sharifah Nurfazilah Wan Yusop 1,  Syahrul Imran 2,  Mohd Ilham Adenan 3,  Sadia Sultan 4
Affiliations

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.
PMID: 32976918 DOI: 10.1016/j.steroids.2020.108735
Abstract

The Fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6β, 20-dihydroxymedroxyprogesterone (2), 12β-hydroxymedroxyprogesterone (3), 6β, 11β-dihydroxymedroxyprogesterone (4), 16β-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6β-hydroxymedroxyprogesterone (9), 15β-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11β-dihydroxy-5α-pregnan-3, 20-dione (11), 11β-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Compounds 12, 5, 6, 9, 11, and 3 (in descending order of activity) also showed some extent of activity against SH-SY5Y tumour cell line. The never been reported biotransformed product, 2, showed the most potent inhibitory activity 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.

Keywords

Acetylcholineterase inhibitors; Anti-proliferative agents; In silico; In vitro; Medroxyprogesterone; Microbial transformation.

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