In vitro and in vivo activity of novel platinum(ii) complexes with naphthalene imide derivatives inhibiting human non-small cell lung cancer cells

Abstract

Four new Pt(II) complexes, [Pt(L^a)]Cl (1), [Pt(L^b)]Cl (2), [Pt(L^c)]Cl (3) and [Pt(L^d)]Cl (4) with the naphthalene imide derivatives L^a–L^d as ligands were designed and prepared. MTT assay indicated that 1–4 exhibited proliferation inhibiting activity against human non-small cell lung cancer (NCI-H460) cells, especially 1–3 showed superior activity (IC₅₀ = 0.10–8.56 μM) compared with cisplatin (IC₅₀ = 12.01 ± 1.03 μM). Various experiments showed that 3 as a telomerase inhibitor induced NCI-H460 cell apoptosis via inhibition of the telomerase and dysfunction of mitochondria. In vivo evaluation results suggested that 3 could significantly inhibit the growth of tumor cells in NCI-H460 tumor-bearing mice and the tumor growth inhibition rate (TGI) reached 40.7%. These results demonstrated that 3 is a telomerase inhibitor and a promising anti-cancer agent.