Applications of Chemometric Methods to Elucidate Physicochemical Requirements for Binding of Cyp51 Inhibitors to Its Target

Abstract

Invasive fungal infection has prevailed in past two decades causing high mortality and morbidity rate, especially in immunocompromised patients. Classical quantitative structure-activity relationship (QSAR analysis) was executed to study correlation between molecular structure and CYP51 inhibitor activity of novel aminotetralin derivatives. A di-parametric model with high statistical values r = 0.84, r2= 0.71, r2cv = 0.60, s = 0.38 and f = 23.56 was generated and validated using leave one out technique and external set of molecules to confirm the predictive power of the generated model. The resultant QSAR model revealed the importance of first atom EState index and VAMP polarization YZ parameters in inhibition of fungal CYP51 enzyme.