Qin Qi-Pin, Wang Zhen-Feng, Huang Xiao-Ling, Tan Ming-Xiong, Shi Bei-Bei, Liang Hong
Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, PR China.
State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
ACS Med Chem Lett. 2019 May 22;10(6):936-940. doi: 10.1021/acsmedchemlett.9b00098. eCollection 2019 Jun 13.
Three novel Ru(II) complexes, namely, (RuCl[L][DMSO])·HO (), (RuCl[L][DMSO]) (), and (RuCl[L][DMSO]) (), which respectively contain 3-(2'-benzimidazolyl)coumarin (L), 3-(2'-benzimidazolyl)-7-fluoro-coumarin (L), and 3-(2'-benzimidazolyl)-7-methoxyl-coumarin (L), were first designed and characterized. showed potent antitumor activity against NCI-H460 cells (IC = 0.30 ± 0.02 μM) and high selectivity between NCI-H460 cancer cells and normal HL-7702 cells. induced NCI-H460 apoptosis via telomerase inhibition, which involved DNA damage, cell-cycle distribution, and S phase-protein down-regulation. However, 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 ligand of . 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 -targeting telomerase anticancer agent.
三种新型钌（II）配合物，即（RuCl[L][DMSO]）·H₂O（）、（RuCl[L][DMSO]）（）和（RuCl[L][DMSO]）（），它们分别含有3-（2'-苯并咪唑基）香豆素（L）、3-（2'-苯并咪唑基）-7-氟香豆素（L）和3-（2'-苯并咪唑基）-7-甲氧基香豆素（L），首次被设计并表征。对NCI-H460细胞显示出强大的抗肿瘤活性（IC₅₀ = 0.30 ± 0.02 μM），并且在NCI-H460癌细胞和正常HL-7702细胞之间具有高选择性。通过抑制端粒酶诱导NCI-H460细胞凋亡，这涉及DNA损伤、细胞周期分布和S期蛋白下调。然而，在NCI-H460细胞中未表现出此类作用，这无疑与L配体中7-氟取代基在中的关键调节作用有关。在NCI-H460异种移植小鼠模型中，与顺铂（抑制率[IR]= 25.5%）相比，表现出相当高的抗癌疗效（抑制率[IR]= 61.3%）。因此，这种香豆素钌（II）化合物是一种有前景的靶向端粒酶抗癌剂。
