QSAR Study Of Substituted N-Containing Hetero Cycles As An Anti-Cancer Agents

Abstract

2D and 3D QSAR analysis were performed on imidazo[4,5-b] pyridine and 4-heteroarylpyrimidine derivatives for their anti-cancer activities on MCF-7 and on HCT-116 cell line. The activity of the imidazo[4,5-b] pyridine and 4-heteroarylpyrimidine on MCF-7 and HCT-116 cell line were converted into -log 1/C. The statistically significant 2D-QSAR models for MCF-7 are r² = 0.8507 and q² = 0.7512 and on HCT-116 giving r² = 0.8238 and q² =0.7267. 3D QSAR study was performed using k-nearest neighbor molecular field analysis (kNN-MFA) approach for electrostatic, steric and hydrophobic fields. Three different kNN-MFA 3D QSAR methods (SW-FB, SA, and GA) were used for the development of models and tested successfully for internal (q² = 0.8625, q²=0.8550) and external (predictive r² = 0.8243, predictive r2 = 0.7582) validation criteria. Thus, 3D QSAR models showed that electrostatic effects dominantly determine the binding affinities. 2D QSAR studies revealed that T_N_O_4 descriptor was major contributing descriptor in case of MCF-7 and T_N_N_3 in case of HCT-116. The 3D QSAR was performed using kNN-MFA method. 3D QSAR results suggested the importance of some molecular characteristics, which should significantly affect the binding affinities of compounds. The results derived may be useful in further designing novel anti-cancer agents.