QSAR Studies of Thiourea, Thiazolidinedione and Thioparabanic Acid Derivatives of 4-Aminoquinoline as Antimalarial Agents

Nitendra K Sahu; Kamlendra S Bhadoriya; Mukesh C Sharma; D V Kohli

Nitendra K Sahu School of Pharmacy, ITM University, Gwalior (MP) 474001, India
Kamlendra S Bhadoriya R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, (MS), 425405 India
Mukesh C Sharma Drug Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (MP),470003 India
D V Kohli Drug Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (MP),470003 India

Abstract

The QSAR studies were performed on a series of thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline to find out the structural requirements of their antimalarial activities. The 2D-QSAR studies were performed using three methods: MLR, giving r2 = 0.7808, q2 = 0.6492 and pred_r2 = 0.9044; the PLS, with r2 = 0.7785, q2 = 0.6420 and pred_r2 = 0.7181; and PCR, giving r2 = 0.7393, q2 = 0.6222 and pred_r2 = 0.9135. The QSAR models showed that the LUMOEnergy, SdsCHE-index and Quadrupole1 played an important role in determining biological activities. The 3D-QSAR studies were performed using the stepwise variable selection k-nearest neighbor molecular field analysis (kNN-MFA) approach; q2 of 0.7107and pred_r2 of 0.8521 were obtained. The results of the present study may be useful for the designing of more potent analogues as antimalarial agents.

Keywords: QSAR, 4-aminoquinoline, antimalarial agents, PLSR, kNN-MFA