QSAR models of antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazoles in various cancer cell lines.

Imidazo[2,1-b][1,3,4]thiadiazoles have been recognized to possess antiproliferative potency towards a wide spectrum of cancer cell lines. QSAR investigations on a set of 42 di(tri)substituted imidazo[2,1-b][1,3,4]thiadiazoles were carried out to find the descriptors determining their biological potency. Three-variable equations were obtained by combinatorial protocols in multiple linear regression (CP MLR) for all three studied cancer cell lines. They showed that lipophilicity, electronic, and steric factors are decisive for the antiproliferative potency of compounds and indicate the important role of nitrogen atoms of imidazothiadiazole ring in the interactions with the molecular target. The best models gave high r squared values in the range from 0.887 to 0.924. They also have good predictive accuracy confirmed by the high value LOO cross-validation coefficient [Formula: see text] (from 0.842 to 0.904) and by the external validation quantities.