3D-QSAR studies on unsaturated 4-azasteroids as human 5α-reductase inhibitors: A self organizing molecular field analysis approach

Abstract

Azasteroids have been reported as inhibitors of human 5α-reductase enzyme. These were designed by substitution of one carbon atom of steroidal A ring by heteroatom nitrogen. Due to lack of information on the crystal structure of human 5α-reductase, 3D-QSAR study has been performed on a series of unsaturated 4-azasteroids using Self Organizing Molecular Field Analysis (SOMFA) for rationalizing the molecular properties and human 5α-reductase inhibitory activities. The statistical results having good cross-validated r2cv (0.783), non cross-validated r2 (0.806) and F-test value (87.282), showed satisfied predictive ability. Analysis of SOMFA models through electrostatic and shape grids provide useful information for the design and optimization of new steroidal human 5α-reductase inhibitors.