GEORGE MIHAI NITULESCU, STEFAN GABRIEL SORIGA, LAURA ILEANA SOCEA, OCTAVIAN TUDOREL OLARU, VALENTIN PLESU STRUCTURE-ACTIVITY RELATIONSHIPS AND CHEMOINFORMATIC ANALYSIS OF THE ANTICANCER PROFILE OF AN AMINOPYRAZOLE DERIVATIVE
In the optimization process of a series of 5-aminopyrazoles candidates in the development of antineoplastic drugs, we used the NCI COMPARE algorithm to predict the mechanism of action of N-<5-(4-bromophenyl)-1H-pyrazol-3-yl>carbamothioyl>benzamide (PZ). Its anti-proliferative profile is corelated with standard antineoplastic drugs. The inhibition of protein kinases emerged as the most probable biological target, especially the glycogen synthase kinase-3 (GSK-3). Several pharmacophore elements and structural descriptors related to the anticancer profile were described. This work provides the framework for the development of new potent GSK-3 inhibitors.
Keywords: COMPARE algorithm, NCI-60 anticancer screening, protein kinases inhibitors, thiourea