title: Generation of comparative pharmacophoric model for steroidal 5α-reductase I and II inhibitors: A 3D-QSAR study on 6-azasteroids.
abstract: Steroidal 5α-reductase, a key enzyme involved in the transformation of testosterone to dihydrotestosterone, is unstable during the purification leading to loss of the activity. Therefore, due to unstable nature, the crystal structure of the 5α-reductase is unknown. In the present study, we have generated a comparative pharmacophoric model for both isoforms of steroidal 5α-reductase using 6-azasteroids. The steric and electrostatic maps generated for both isoforms provides structure framework for designing of new inhibitors. Further, 3D-maps are also helpful in understanding variability in the activity of the compounds. Statistical measures generated for both enzymes showed good internal and external prediction. Overall, the analyses of models provides structural requirement of dual and selective steroidal 5α-reductase inhibitors in an interactive fashion.
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur, C.G. 495 009, India. Electronic address: sureshthareja@gmail.com.
authors.forename: Suresh
authors.initials: S
authors.lastname: Thareja
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur, C.G. 495 009, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Rajpoot
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur, C.G. 495 009, India.
authors.forename: Sant K
authors.initials: SK
authors.lastname: Verma
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D001378:Azasteroids / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
keywords: 3D-QSAR; 5α-Reductase; 6-Azasteroids; Pharmacophore; SOMFA