title: New biaryl-chalcone derivatives of pregnenolone via Suzuki-Miyaura cross-coupling reaction. Synthesis, CYP17 hydroxylase inhibition activity, QSAR, and molecular docking study.
abstract: A new class of steroids is being synthesized for its ability to prevent intratumoral androgen production by inhibiting the activity of CYP17 hydroxylase enzyme. The scheme involved the synthesis of chalcone derivative of pregnenolone 5 which was further modified to the corresponding biaryl-chalcone pregnenolone analogs 16-25 using Suzuki-Miyaura cross-coupling reaction. The synthesized compounds were tested for activity using human CYP17α hydroxylase expressed in Escherichia coli. Compounds 21 was the most active inhibitor in this series, with IC50 values of 0.61μM and selectivity profile of 88.7% inhibition of hydroxylase enzyme. Molecular docking study of 21 was performed and showed the hydrogen bonds and hydrophobic interaction with the amino acid residues of the active site of CYP17.
authors.affiliation: Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq. 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: Rawaa A
authors.initials: RA
authors.lastname: Kadhim
authors.affiliation: Department of Chemistry, College of Science, 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: Matthias
authors.initials: M
authors.lastname: Engel
mesh_terms: D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives*; D060326:Chemistry Techniques, Synthetic; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D011284:Pregnenolone / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D002599:Chalcone; D011284:Pregnenolone; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP17 hydroxylase enzyme; Molecular docking study; Pregnenolone; QSAR; Suzuki–Miyaura cross-coupling reaction