Synthesis and antitumor evaluation of fluoroquinolon C3 s-triazole oxadiazole methylsulfide derivatives of ofloxacin / 中国药学杂志

ABSTRACT

OBJECTIVE: To explore an efficient heterocyclic bioisostere as the C3 carboxylic group of antibacterial fluoroquinolones for further development of antitumor fluoroquinolones. METHODS: Using the s-triazole ring as an isosteric replacement of the C3 carboxylic group with another different heterocyclic ring, oxadiazole, as a modified group, new bis-(different azole) methylsulfide derivatives, 6-fluoro-7-(4-methyl-piperazin-1-yl)-1, 8-(2, 1-oxpropyl)-5-[5-(aryl-[1, 3, 4]-oxadiazol-2-methylsulfanyl)-4H-[1, 2, 4]-tri-azol-3yl]-quinolin-4(1H)-ones (6a-6j), were designed from ofloxacin (1). The in vitro antitumor activity of 6a-6j against three cancer cell lines was evaluated by MTT assay. RESULTS: Ten title compounds (6a-6j) ere synthesized and their structures were characterized by spectral data. They exhibited significantly higher in vitro antitumor potency than the parent compound ofloxacin. CONCLUSION: The heterocyclic ring, s-triazole, could be used as an efficient isostere of the C-3 carboxylic group for further development of antitumor fluoroquinolone candidates.