Statistical analysis of the impact of molecular descriptors on cytotoxicity of thiourea derivatives incorporating 2-aminothiazole scaffold

Chemical reactivity descriptors and lipophilicyty (logP) were evaluated via semi-empirical method for the quantum calculation of molecular electronic structure (PM3) in order to clarify the structure-cytotoxic activity relationships of disubstutited thioureas. Analysed compounds were obtained by the linkage of 2-aminothiazole ring, thiourea and substituted phenyl ring. The detailed examination was carried out to establish correlation between descriptors and cytotoxic activity against the MT-4 cells for 11 compounds. For the most active compounds (6 compounds) cytotoxic activity against three cancer cell lines (CCRF-CEM, WIL-2NS, CCRF-SB) and normal human cell (HaCaT) was determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release were assessed. Regression analysis revealed that electrophilicity index and chemical potential significantly contributed to expain the thioureas cytotoxic potential.