Triazine-benzimidazole hybrids: Anticancer activity, DNA interaction and dihydrofolate reductase inhibitors

A new series of triazine-benzimidazole hybrids has been synthesized with different substitution of primary and secondary amines at one of the position of triazine in moderate to good yields. These compounds were evaluated for their inhibitory activities over 60 human tumor cell lines at one dose and five dose concentrations. Compounds 6b, 8 and 9 showed broad spectrum of antitumor activities with GI(50) values of 9.79, 2.58 and 3.81 mu M, respectively. DNA binding studies also indicated strong interaction properties of these compounds. These synthesized compounds also showed inhibition of mammalian dihydrofolate reductase (DHFR). Compound 6b was depicted as the most active member of DHFR inhibitor with IC50 value of 1.05 mu M. Molecular modelling studies were used to identify the stabilized interactions of Compound 6b within the active site of enzyme for DHFR. (C) 2015 Elsevier Ltd. All rights reserved.