Synthesis, cytotoxicity and structure-activity relationships between ester and amide functionalities in novel acridine-based platinum(II) complexes

In order to improve the pharmacological profile of the anticancer drug cisplatin, several new acridine-based tethered (ethane-1,2-diamine)platinum(II) complexes connected by a polymethylene chain were synthetized. Activity-structure relationship between amide or ester functionalities was explored by changing acridine-9-carboxamide into acridine-9-carboxylate chromophore. The in vitro cytotoxicity of these new complexes was assessed in human colic HCT 116, SW480 and HT-29 cancer cell lines. Series of complexes bearing the acridine-9-carboxylate chromophore displayed higher cytotoxic effect than acridine-9-carboxamide complexes, with gradual effect according to the size of the polymethylene linker.

A panel of new cisplatin-like complexes containing acridine derivatives was synthesized. Activity-structure relationship between amide or ester functionalities and the size of the polymethylene linker were explored.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of 9-substituted acridine–platinum(II) complexes.
► Influence of ester and amide functionalities and of the size of polymethylene chain.
► In vitro cytotoxicity in human colic cancer cell lines.
► Acridine-9-carboxylate complexes displayed the highest cytotoxic effect.