2. Academic Validation
  3. Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors

Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors

  • Bioorg Med Chem. 2016 Feb 15;24(4):779-88. doi: 10.1016/j.bmc.2015.12.048.
Saurabh Aggarwal 1,  Manoj Kumar Mahapatra 1,  Rajnish Kumar 1,  Tilak R Bhardwaj 2,  Rolf W Hartmann 3,  Jörg Haupenthal 4,  Manoj Kumar 5
Affiliations

Affiliations

  • 1 University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
  • 2 University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India; School of Pharmacy & Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, Himachal Pradesh, India.
  • 3 Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus 81, D-66123 Saarbrücken, Germany; Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, Saarbrücken, Germany.
  • 4 Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus 81, D-66123 Saarbrücken, Germany.
  • 5 University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: manoj_uips@pu.ac.in.
PMID: 26780831 DOI: 10.1016/j.bmc.2015.12.048
Abstract

In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one (6), 3-tetrazolo-19-nor-3,5-androstadien-17-one (10), 3-tetrazolo-3,5-pregnadien-20-one (14), 17a-substituted 3-tetrazolo-17a-aza-D-homo-3,5-androstadien-17-one (26-31) and 3-(2-acetyltetrazolo)-17a-aza-d-homo-3,5-androstadien-17-one (32) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction (p <0.05) in rat prostate weight. The most potent compound 14 showed 5AR-2 inhibition with IC50 being 15.6nM as compared to clinically used drug finasteride (40nM). There was also a significant inhibition of 5AR-1 with IC50 547nM compared to finasteride (453nM).

Keywords

5AR; Finasteride; HEK; Testosterone; Tetrazole.

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