Synthesis of new Pyridoclax analogs: Insights into their druggability through investigation of their physicochemical properties and their interactions with membranes

Pyridoclax is considered as a promising anticancer drug, acting as a protein-protein interactions disruptor, with potential applications in the treatment of ovarian, lung, and mesothelioma cancers. 18 sensibly selected structural analogs of Pyridoclax were synthesized, and their physico-chemical properties were systematically assessed, and analyzed. Moreover, considering that drug-membrane interactions play an essential role to understand drugs mode of action and eventual toxic effects, membrane models were used to investigate such interactions in the bulk (liposomes) and at the air-water interface. The measured experimental data on all original oligopyridines have permitted to assess relative differences in terms of physico-chemical properties which could be determinant for their druggability, and hence for their drug development.