A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

Najim A Al-Masoudi; Kuthiar M Mahdi; Nabeel A Abdul-Rida; Bahjat A Saeed; Mathias Engel

doi:10.1016/j.steroids.2015.05.002

A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

Steroids. 2015 Aug:100:52-9. doi: 10.1016/j.steroids.2015.05.002. Epub 2015 May 16.

Authors

Najim A Al-Masoudi¹, Kuthiar M Mahdi², Nabeel A Abdul-Rida², Bahjat A Saeed³, Mathias Engel⁴

Affiliations

¹ Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq; Am Tannenhof 8, 78464 Konstanz, Germany. Electronic address: najim.al-masoudi@gmx.de.
² Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, Iraq.
³ Department of Chemistry, College of Education, University of Basrah, Basrah, Iraq.
⁴ Institut für Pharmazeutische und Medizinische Chemie, Universität des Saarlandes, Saarbrücken, Germany.

PMID: 25988615
DOI: 10.1016/j.steroids.2015.05.002

Abstract

A new series of 17-(N-(arylimino)-5-pregnen-3β-ol derivatives 19-32 as well as carboxylate and acrylate analogues of pregnenolone 37-40 were synthesized and evaluated for their inhibitory activity against human CYP17 hydroxylase expressed in Escherichia coli. Compounds 32 and 37 were the most potent analogues in this series, showing inhibition activity with IC50 = 2.11 and 1.29 μM, respectively. However, the analogue 37 revealed a better selectivity profile (83.21% inhibition of hydroxylase), which is a leading candidate for further development. Molecular docking study of 37 showed binding with the amino acid residues of CYP17 through hydrogen bonds and hydrophobic interaction.

Keywords: CYP17 hydroxylase; Imine analogues; Molecular docking; Pregnenolone; Prostate cancer.

Publication types

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

MeSH terms

Binding Sites
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Molecular Docking Simulation
Pregnenolone / analogs & derivatives*
Pregnenolone / chemical synthesis*
Pregnenolone / chemistry
Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
Steroid 17-alpha-Hydroxylase / chemistry

Substances

Pregnenolone
Steroid 17-alpha-Hydroxylase