High in Vitro and in Vivo Tumor-Selective Novel Ruthenium(II) Complexes with 3-(2'-Benzimidazolyl)-7-fluoro-coumarin

Qi-Pin Qin; Zhen-Feng Wang; Xiao-Ling Huang; Ming-Xiong Tan; Bei-Bei Shi; Hong Liang

doi:10.1021/acsmedchemlett.9b00098

High in Vitro and in Vivo Tumor-Selective Novel Ruthenium(II) Complexes with 3-(2'-Benzimidazolyl)-7-fluoro-coumarin

ACS Med Chem Lett. 2019 May 22;10(6):936-940. doi: 10.1021/acsmedchemlett.9b00098. eCollection 2019 Jun 13.

Authors

Qi-Pin Qin¹, Zhen-Feng Wang¹, Xiao-Ling Huang¹, Ming-Xiong Tan¹, Bei-Bei Shi¹, Hong Liang²

Affiliations

¹ 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.
² 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.

Abstract

Three novel Ru(II) complexes, namely, (RuCl₂[L^a][DMSO]₂)·H₂O (Ru1), (RuCl₂[L^b][DMSO]₂) (Ru2), and (RuCl₂[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 (IC₅₀ = 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.