Synthesis and antitumor mechanisms of two new 8-hydroxyquinoline platinum(ii) derivatives

Abstract

Herein, we report the design and synthesis of two new 8-hydroxyquinoline platinum(II) derivatives, namely [Pt(QCl)Cl₂]·CH₃OH (YLN1, YLN = Yulin Normal University) and [Pt(QBr)Cl₂]·CH₃OH (YLN2), with 2-[(5-chloropyridin-2-yl)-hydrazonomethyl]-quinolin-8-ol (QCl) and 2-[(5-bromopyridin-2-yl)-hydrazonomethyl]-quinolin-8-ol (QBr) as ligands, respectively. The cytotoxicity of YLN1 and YLN2 against MDA-MB-231 breast cancer cells (IC₅₀ = 5.49 ± 0.14 μM and 7.09 ± 0.24 μM) was found to be generally higher than against noncancer HL-7702 cells (IC₅₀ > 20.0 μM). Moreover, YLN1 and YLN2 induced senescence and apoptosis in MDA-MB-231 (MM231) cancer cells by significantly triggering DNA damage and downregulating hTERT mRNA expression, and the antitumor mechanisms of the Pt(II) complexes with different QCl and QBr ligands follows the order of YLN1 > YLN2. Taken together, we found the two new 8-hydroxyquinoline platinum(II) derivatives YLN1 and YLN2 as specific anticancer drugs targeting DNA damage response and hTERT suppression.