ABSTRACT
Fluoroquinolones are potent inhibitors of bacterial topoisomerase II. They can also inhibit eukaryotic topoisomerase, and may confer antitumoral properties. In this study the antitumoral activity of a new series of N-substituted piperazinyl- fluoroquinolones against a panel of human tumor cell lines was determined by MTT assays. Among the tested compounds N-[2- [5-bromo-2-thienyl]-2-oxoethyl] [C1,N1,E1], N-[2- [5-bromo-2-thienyl]-2-[hydroxyimino] ethyl][C2,N2,E2] and N-[2-[5-bromo-2-thienyl]-2-[phenylmethoxyimino] ethyl] [C3,N3,E3] piperazinyl quinolones exhibited the most cytotoxic activities [mean IC50s = 2.5 to 3 microg/ml], comparable to that of the Etoposide [mean IC50= 1.7micro g/ml]. Replacement of the 5- bromo-2-thienyl with 4- fluorophenyl or 2, 6- 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. These data suggest that these series of quinolones provide good models for the further design of potent antitumor compounds