Bioisosteric modification of known fucosidase inhibitors A and B, resulted in three new types of molecules, 4b, 5c and 6a (belonging to furopyridinedione, thiohydantoin and hydantoin chemotypes) that could potentially bind to a-L-fucosidase (bovine kidney origin). Molecular docking revealed and compared the putative binding interaction between 4b, 5c and 6a with A and B against the active site of a homology model of a-L-fucosidase. Based on this initial investigation, design and synthesis of a library of small molecules based on furopyridinedione, thiohydantoin and hydantoin, followed by their in vitro screening against a-L-fucosidase (bovine kidney origin) generated a potent inhibitor (compound 4e) with IC 50 of $0.7 mM. Compound 4e possessed no cytotoxic properties when tested against healthy mammalian COS-1 cells. Reaction kinetics study suggested it to be a mixed inhibitor. Finally compounds 4a, b, e and f, bearing the furopyridinedione motif also exhibited substantial inhibition of the proliferation of MCF 7 breast cancer cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.