Steroidal 5¦Á-reductase Inhibitors Quantum Chemistry And Quantitative Structure-activity Relationship Study

The reduction of testosterone (T) to the dihydrotestosterone (DHT) is catalyzed by NADPH-dependent enzyme of steroid 5 a -reductase. DHT is considered as the most potent male sex hermone in the body. High levels of DHT is related to disorders such as BPH(benign prostatic hyperplasia), prostatic cancer, acne, pattern baldness and alopecia. Therefore, the blockade of formation of DHT by using enzyme inhibitors is a importance way in treating disorders related to high levels of DHT.In this paper, 55 analogs steroid compounds of 5 a -reductase enzyme( I ) inhibitors have been calculated by use of molecular mechanics and quantum chemistry methods AMI. We obtained a lot of data about molecular structure parameter and quantum chemistry parameter. We try to research for the relationships between activity and structure, explore the action mechanism of drugs.l)As for the compounds, site at 4,6 are the possible active area where drugs interacts with enzyme. The hydrogen-bond between O-21 of T or compounds and enzyme can be formed and explained it from Frontier Orbital densities and charges,stereo effect. From the average distribution of LUMO densities, We explained that the activity is decreased when unsaturation bond is located at site 1,2 or 5,6.2)The hydrophobicity is an important factor to affect the bioactivity in a non-linear way. We confirmed it by ANN(artificial neural network). The factors to affect the hydrophobicity were studied and discussed.3)We discussed the relationships between activity and structure. The significant QSAR models were set up. The stereo effect and hydrophobicity of molecular and substituents, the charge at site C-17 are the mainly factors to affect the activity.Our results can be helpful to both drugs synthesize and drugs action mechnism.