International Journal of Drug Discovery

63-73

Authors: MUKESH YADAV, ANURAJ NAYARISSERI, SHOBHA JOSHI, ANKITA GUPTA, PURVA HOLKAR, ASHISH RAJPUT

QSAR studies of thirty 2-arylbenzoxazole derivatives are carried out to probe their inhibitory activity against Cholesteryl Ester Transfer Protein (CETP). QSAR models have been obtained using multiple linear regression (MLR) analysis after manifestation of forward selection algorithm to cull significant descriptors out of descriptor’s pool. QSAR models are elected with adherent set of statistical parameters with R2=0.9431 and R2=0.9069. Validation of modeling includes method of Y-Scrambling and in addition to this, some other methods of validation. Moreover, QSAR approach of 2-arylbenzoxazoles are also attempted, supported and validated by flexible docking studies as well. The search strategies include evolutionary algorithm and edited form of Gehlhaar PLP scoring function. The same set of thirty candidates from 2-arylbenzoxazole derivatives is processed in molecular docking and their docking scores are found in agreement with QSAR studies reported. Remarkable CETP inhibitory activity is exhibited by a 2-arylbenzoxazole derivatives molecule 29C with most comprehensive set of interactions with rerank scores -102.167 and RMSD values 1.104. Hydrogen bond interactions along with hydrophobic and electrostatic interactions are mapped to confirm their potencies.