Self organizing molecular field analysis on a series of human 5alpha-reductase inhibitors: unsaturated 3-carboxysteroid.
Steroidal 5alpha-reductase is a NADPH dependent enzyme that catalyzes the irreversible conversion of 4-en-3-oxo-steroid testosterone to the corresponding 5alpha-H-3-oxo-steroid dihydrotestosterone thus involved in Benign Prostatic Hyperplasia (BPH). As the crystal structure of target enzyme is not available; we have carried out ligand based designing using Self Organizing Molecular Field Analysis (SOMFA). SOMFA, a novel 3D-QSAR methodology used in present case to study the correlation between molecular properties and human 5alpha-reductase inhibitory activities of a series of unsaturated 3-carboxysteroid. The statistical results, good cross-validated r(2)(cv) (0.693) and non cross-validated r(2) (0.732), showed satisfied predictive ability. All analysis of SOMFA model may provide some useful information in the design of human steroidal 5alpha-reductase inhibitors with better spectrum of activity.
Thareja
Suresh
S
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Aggarwal
Saurabh
S
Bhardwaj
T R
TR
Kumar
Manoj
M
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology*; D003198:Computer Simulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors