Synthesis of 8-carboxamide-substituted angelicin derivatives

A method for the synthesis of 4-methyl-2-oxo-9-phenyl-2 H -furo[2,3- h ]chromene-8-carboxylic acid amides combining in the structure the angelicin core with heterocyclic fragments at the amide nitrogen atom was developed. The cytotoxic activity of the obtained amides against the MCF7 (breast adenocarcinoma), A549 (non-small cell lung cancer), VA-13 (embryonic lung fibroblast cells) and HEK293T (embryonic kidney cells) cell lines was studied. In contrast to the previously described highly toxic angelicin derivatives with aryl- and hetarylcarbonyl substituents at position 8, the synthesized amides demonstrated in in vitro experiments in these cell lines the IC 50abs values ranging within 2–100 µmol L −1 . The cytotoxicity and selectivity of the action of this group of derivatives were found to be significantly affected by the substituent at position 5′ of the angelicin moiety.