title: A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study.
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.
authors.affiliation: Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq; Am Tannenhof 8, 78464 Konstanz, Germany. Electronic address: najim.al-masoudi@gmx.de.
authors.forename: Najim A
authors.initials: NA
authors.lastname: Al-Masoudi
authors.affiliation: Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, Iraq.
authors.forename: Kuthiar M
authors.initials: KM
authors.lastname: Mahdi
authors.affiliation: Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, Iraq.
authors.forename: Nabeel A
authors.initials: NA
authors.lastname: Abdul-Rida
authors.affiliation: Department of Chemistry, College of Education, University of Basrah, Basrah, Iraq.
authors.forename: Bahjat A
authors.initials: BA
authors.lastname: Saeed
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Universität des Saarlandes, Saarbrücken, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Engel
mesh_terms: D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D011284:Pregnenolone; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP17 hydroxylase; Imine analogues; Molecular docking; Pregnenolone; Prostate cancer