2D-QSAR Studies on Unsaturated 4-Azasteroids as 5α-reductase Inhibitors

Abstract

Abstract

Dihydrotestosterone (DHT) a major circulating male hormone is produced by NADPH dependent enzyme 5α-reductase (5 alpha R) and has been found to be causative agent in the development of pathological condition i.e. benign prostate hyperplasia (BPH). Thus inhibition of 5α-reductase enzyme represents a novel target in the treatment of BPH. Present study describes the relationship between the 5α-Reductase inhibitory activity for structurally related unsaturated 4-azasteroids derivatives and their physicochemical descriptors in quantitative terms. Using Vlife molecular design suits (MDS), LOO validated 2D-QSAR model has been developed with statistical data r² = 0.8706, q² =0.7122 , F = 14.5758, pred r² = 0.7441. Descriptor with positive and negative correlation with the biological activity has been highlighted. This validated 2D-QSAR model may be used to design 5α-Reductase derivatives with better inhibitory properties.

Graphical Abstract

pIC50 = +0.0094(Quadrupole1)-0.2285(SssCH2E-index)-0.3929(chi4pathCluster)-0.0724(5PathCount)+0.0240(SA Hydrophilic Area)+5.3457(Id Average)-0.23550

Keywords: Dihydrotestosterone, benign prostatic hyperplasia, 5α-reductase inhibitors, 2D-QSAR, regression analysis, 4-azasteroids

Cite this Article

Priyanka Rana, Richa Dhingra, Monika et al. 2D-QSAR Studies on Unsaturated 4-Azasteroids as 5α-Reductase Inhibitors. Research & Reviews: A Journal of Drug Design & Discovery. 2017; 4(1): 26–37p.