Abstract
Three novel Ru(II) complexes, namely, (RuCl(2)[L(a)][DMSO](2))·H(2)O (Ru1), (RuCl(2)[L(b)][DMSO](2)) (Ru2), and (RuCl(2)[L(c)][DMSO](2)) (Ru3), which respectively contain 3-(2'-benzimidazolyl)coumarin (L(a)), 3-(2'-benzimidazolyl)-7-fluoro-coumarin (L(b)), and 3-(2'-benzimidazolyl)-7-methoxyl-coumarin (L(c)), were first designed and characterized. Ru2 showed potent antitumor activity against NCI-H460 cells (IC(50) = 0.30 ± 0.02 μM) and high selectivity between NCI-H460 cancer cells and normal HL-7702 cells. Ru2 induced NCI-H460 apoptosis via telomerase inhibition, which involved DNA damage, cell-cycle distribution, and S phase-protein down-regulation. However, Ru1 did not demonstrate such effects in NCI-H460 cells, which is undoubtedly associated with the key regulatory role of the 7-fluoro substituted group in the L(b) ligand of Ru2. Ru2 exhibited considerably higher anticancer efficacy (inhibition rate [IR] = 61.3%) compared with cisplatin (IR= 25.5%) in a NCI-H460 xenograft mouse model. Thus, this coumarin Ru(II) compound is a promising Ru2-targeting telomerase anticancer agent.