Design, synthesis and in vitro cytotoxicity evaluation of new fluorinated ionic salt (S)-(+)-2,3-Dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione as strategies for improving anticonvulsant activity

Abstract

The reaction of (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (1) with 4-(trifluoromethyl)benzoic acid (2, C8H5F3O2) in dimethylformamide leads to the formation of C8H5F3O2 (1) as a classical ionic salt 3. The structure of new compound has been characterized by FTIR, 1H NMR, 13C NMR, HRMS spectroscopy. The new compound was tested for in vitro cytotoxicity evaluation by MTT assay against breast adenocarcinoma cell line of MCF-7 cells. A new compound 3 (IC50:199 µM) emerged as minimal toxic when compared to clinical drugs carbamazepine, topiramate and benzodiazepine. A preliminary study of structure activity relationship revealed that the incorporation of fluoro or trifluoromethyl moiety into the compound, even through ionic bond formation, had a great effect on the biological activity and with less toxicity or side effects.