2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases.

ABSTRACT: We have carried out the design, synthesis, and evaluation of a small library of 2-aminobenzoxazole-appended coumarins as novel inhibitors of tumour-related CAs IX and XII. Substituents on C-3 and/or C-4 positions of the coumarin scaffold, and on the benzoxazole moiety, together with the length of the linker connecting both units were modified to obtain useful structure-activity relationships. CA inhibition studies revealed a good selectivity towards tumour-associated CAs IX and XII (K_i within the mid-nanomolar range in most of the cases) in comparison with CAs I, II, IV, and VII (K_i > 10 µM); CA IX was found to be slightly more sensitive towards structural changes. Docking calculations suggested that the coumarin scaffold might act as a prodrug, binding

SUBMITTER: Fuentes-Aguilar A 

PROVIDER: S-EPMC8667885 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature