In Vitro Cytotoxicity Evaluation of Sixteen New N-Piperazinyl Quinolone Derivatives Against A Panel Of Tumor Cell Lines

Introduction: Fluoroquinolones are potent inhibitors of bacterial topoisomerase II. They can also inhibit eukaryotic topoisomerase, and may confer antitumoral properties. Method: In this study the antitumoral activity of a new series of N-substituted piperazinylfluoroquinolones against a panel of human tumor cell lines was determined by MTT assays. Results: Among the tested compounds N-[۲- (۵-bromo-۲-thienyl)-۲-oxoethyl ] (C۱,N۱,E۱), N-[ ۲- (۵-bromo-۲-thienyl)-۲-(hydroxyimino) ethyl]( C۲,N۲,E۲) and N-[۲-(۵-bromo-۲-thienyl)-۲- (phenylmethoxyimino) ethyl] (C۳,N۳,E۳) piperazinyl quinolones exhibited the most cytotoxic activities (mean IC۵۰s = ۲.۵ to ۳ µg/ml), comparable to that of the Etoposide (mean IC۵۰= ۱.۷µg/ml). Replacement of the ۵- bromo-۲-thienyl with ۴- fluorophenyl or ۲,۶- difluorophenyl rings leads to variable inhibition activity. The quinolone activity was enhanced by the presence of a chlorine and two fluorine atoms at the benzyl and phenyl groups, especially against ACHN renal adenocarcinoma cell line. Conclusion: These data suggest that these series of quinolones provide good models for the further design of potent antitumor compounds.

Keywords:

Cytotoxicity , Fluoroquinolone , MTT- assay , Etoposide