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Abstract In the present study, one novel Pt(II) complex, [Pt(CTD)(DMSO)Cl 2 ] (1) with 9‑chloro‑5,6,7,8‑tetrahydroacridine (CTD) as ligand, was synthesized and fully characterized. The CTD Pt(II) complex 1 was an anti-cancer drug candidate, and it possessed potent therapeutic efficacy for hepatocellular carcinoma (HCC). To explore its mechanism against HCC, Hep‑G2 cells were treated with the CTD Pt(II) complex 1 in vitro. MTT assay showed that the CTD Pt(II) complex 1 had inhibitory activity against five human cancer cells, such as SK‑OV‑3, Hep‑G2, NCI‑H460, MGC80‑3 and HL‑7702, and it displayed the strongest inhibitory activity against Hep‑G2 cells with an IC 50 value of 10.48 ± 0.83 μM. Moreover, the CTD Pt(II) complex 1 also exhibited selective cytotoxicity toward the cancer cells. In addition, the CTD Pt(II) complex 1 had low toxicity against non-cancerous HL‑7702 cells. The CTD Pt(II) complex 1 caused mitochondrial dysfunction, leading to the down-regulation of bcl‑2 protein and up-regulation of some mitochondria-initiated apoptotic proteins (including apaf‑1, cytochrome c and bax) in Hep‑G2 cells. Taken together, the CTD Pt(II) complex 1 -triggered Hep‑G2 cell apoptosis was mainly mediated via interaction with c‑myc promoter and disruption of mitochondrial pathway. Collectively, our findings supported that the CTD Pt(II) complex 1 could be used as a potential drug candidate for chemoprevention or chemotherapy of HCC. Graphical abstract The CTD Pt(II) complex 1 triggered Hep‑G2 cell apoptosis mainly through inhibiting telomerase activity by interacting with c‑myc promoter elements and disruption of mitochondrial pathway. Unlabelled Image Highlights • The CTD Pt(II) complex 1 with 9‑chloro‑5,6,7,8‑tetrahydroacridine was designed and synthesized. • The CTD Pt(II) complex 1 was more selective for Hep‑G2 tumor cells versus normal cells (HL‑7702). • The CTD Pt(II) complex 1 was a potent inhibitor of telomerase. • The CTD Pt(II) complex 1 also caused mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Graphical abstract Pt(II) complex 1- induced mitochondrial dysfunction could be an valuable target for the development of new anticancer drugs. Abstract Two new Pt(II) and Ru(II) complexes, [Pt(BFCY)Cl 2 ] (1) and [RuCl 2 (BMCY)(DMSO)] (2) with 3-(1H-benzoimidazol-2-yl)-8-fluoro-chromen-2-ylideneamine (BFCY) and 3-(1H-benzoimidazol-2-yl)-8-methyl-chromen-2-ylideneamine (BMCY), were synthesized. The BFCY Pt(II) complex 1 adopted an approximately four-coordinated square planar geometry, while BMCY complex 2 formed a distorted octahedral geometry. Among the seven selected human cancer cell lines, the two new Pt(II) and Ru(II) complexes 1 and 2 exhibited more potent activities against cisplatin-resistant SK-OV-3/DDP tumor cells (IC 50 = 2.08 ± 1.04 μM and 18.06 ± 0.36 μM, respectively), compared with the free BFCY and BMCY ligands as well as cisplatin. In addition, the BFCY Pt(II) complex 1 could induce cell cycle arrest in S phase and regulate the S-phase cell cycle-related proteins. Remarkably, the BFCY Pt(II) complex 1 also induced mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]