Abstract A010: Anticancer activity as a function of ligand isomerism in the series Pt(CH3)2I2{2,2'-bipyridine-n,n'-(CH3)2} (n,n' = 4,4'; 5,5'; and 6,6')

Abstract Several organoplatinum(IV) complexes have been reported to exhibit pronounced in vitro cytotoxicity against diverse cancer cell lines. Electronically and coordinatively saturated platinum(IV) compounds are more inert than unsaturated platinum(II) compounds, and so they tend to undergo fewer unwanted side reactions in plasma and cellular environments - making them potentially safer chemotherapy drugs. Furthermore, the organic ligands in organoplatinum drugs impart lipophilicity to the drug, enabling the drug to diffuse through the cell membrane more easily. This present poster describes the in vitro anticancer activity of the series of organoplatinum(IV) complexes Pt(CH3)2I2{2,2'-bipyridine-n,n'-(CH3)2} (n,n' = 4,4'; 5,5'; and 6,6'). The 5,5' and 6,6' isomers were structurally characterized by single crystal X-ray diffraction. All three isomers as well as Pt(CH3)2I2{2,2'-bipyridine} were assessed in vitro as anticancer drugs against 60 cancer cell lines. While the cytotoxicities of Pt(CH3)2I2{2,2'-bipyridine} and the 4,4' and 5,5' isomers were limited for the most part, the anticancer effectiveness of Pt(CH3)2I2{2,2'-bipyridine-6,6'-(CH3)2} was significantly more pronounced. For instance, LC50 = 8.17 micromolar against human colon cancer cell line HCT-116; and LC50 = 7.34 micromolar against human ovarian cancer cell line OVCAR-3. The heightened cytotoxicity of Pt(CH3)2I2{2,2'-bipyridine-6,6'-(CH3)2} is explained, at least in part, by the facile dissociation of the 2,2'-bipyridine-6,6'-dimethyl ligand from the platinum (IV) center. Citation Format: William A. Howard, Shadrach J. Stitz, Dongwook Kim, Kraig A. Wheeler. Anticancer activity as a function of ligand isomerism in the series Pt(CH3)2I2{2,2'-bipyridine-n,n'-(CH3)2} (n,n' = 4,4'; 5,5'; and 6,6') [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr A010.