Imidazo [2, 1-b][1,3,4] Thiadiazoles as Murine Leukemia Cell Inhibitors: Quantitative Structure Activity Relationship (Qsar) Study

Abstract

Structure activity relationship study was done on imidazo[2,1-b][1,3,4]thaidiazole derivatives. It shows substitution with –CHO group and Coumarin results in more active compounds than H, Br or SCN group and aryl group. Objective of the present study is to establish quantitative structure activity relationship (QSAR) between physicochemical properties of the selected series and murine leukemia cell inhibitory activity. The present study showed good correlation between Murine leukemic cell inhibitory activity and the descriptors partition coefficient (PC), cluster count (ClsC) and principal moment of inertia about X-axis (PMI-X). Most significant model was found to have squared correlation coefficient (r2), cross validated correlation coefficient (q2) and predictive correlation coefficient (pred r2) 0.72, 0.56 and 0.72 respectively. The negative coefficient value for partition coefficient and principal moment of inertia indicate that lesser value lead to better murine leukemia cell inhibitory activity where as higher value leads to decrease in activity. Positive coefficient value of Cluster count indicates that higher value leads to better biological activity whereas lower value leads to decrease in activity. Toxicity and molecular properties were also calculated for the active compounds. It indicates that –SCN derivatives are toxic (5d, 5i). Compounds 2d, 3i, 4c and 4i showed no indication for toxicity. Compound 2d showed highest Druglikeness (5.11) and Drug Score (0.76), although pIC₅₀ is less. The most active compound 4i showed Druglikeness and Drug Score, 4.34 and 0.67 respectively.