Abstract A003: In vitro anticancer activities of some organoplatinum (IV) derivatives

Abstract

Abstract Recent investigations into organoplatinum (IV) complexes as potential anticancer agents have shown considerable promise. Unlike cisplatin, these compounds are more stable in physiological environments and generally exhibit fewer side effects. Additionally, chelating aromatic ancillary ligands have been found to enhance the intercalation of metal-based agents into tumor DNA. This study aimed to synthesize novel organoplatinum (IV) complexes with chelating aromatic ligands and evaluate their anticancer efficacy through in vitro assays. Five complexes were synthesized: [Pt(CH3)2X2{2,2’-bipyridine-4,4’-R2}] (X = Br, I; R = H, CO2H) and [{Pt(CH3)3}2(μ-I)2(μ-adenine)]. These were characterized by single crystal X-ray diffraction and assessed for anticancer activity. The MTT assays indicated that the [Pt(CH3)2X2{2,2’-bipyridine}] complexes were more cytotoxic to the ZR-75-1 human breast cancer cell line than cisplatin, with LC50 values of 6.1 µM for X = I, 11.5 µM for X = Br, compared to 16.4 µM for cisplatin. Furthermore, the sulforhodamine B assays conducted by the National Cancer Institute's Developmental Therapeutics Program revealed that [Pt(CH3)3}2(μ-I)2(μ-adenine)] was highly effective against various cancer cell lines. Notably, it showed an LC50 value of 5.20 µM against the glioblastoma multiforme SF-539 cell line, whereas cisplatin and temozolomide had LC50 values exceeding 100 µM. Similarly, [Pt(CH3)3}2(μ-I)2(μ-adenine)] had an LC50 value of 5.99 µM against the renal carcinoma RXF-393 cell line, with cisplatin and cabozantinib showing LC50 values above 100 µM. While these results highlight the superior cytotoxicity of the tested organoplatinum (IV) complexes, further research and development are required before these compounds can be considered for commercial use as chemotherapy drugs. Citation Format: William A. Howard. In vitro anticancer activities of some organoplatinum (IV) derivatives [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A003