Synthesis and antitumor activity of fluoroquinolone C-3 fused heterocyclic thiazolo3, 2-b 1, 2, 4triazole derivatives (VI) / 中国药学杂志

ABSTRACT

OBJECTIVE: To discover an efficient strategy for conversion of the antibacterial activity of fluoroquinolone drugs to antitumor activity. METHODS: Novel title fused heterocyclic C-3 thiazolo[3,2-6] [1,2,4] triazole derivatives(5,6) were designed by using a s-triazole ring as the bioisostere and modifying it by a fused condensation-cyclization reaction. The structures were validated by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against three tested tumor cell lines was evaluated by MTT assay. RESULTS: Twelve title compounds were synthesized from ofloxacin and exhibited more significant antiproliferative activity than both of parent ofloxacin 1 and the corresponding intermediate sulfide ketones 5, but displayed a slightly weaker activity than the corresponding sulfide ketone thiosemi-carbazones 6. CONCLUSION: An efficient structure modification strategy for the fused heterocyclic core of thiazolotriazole used as the C-3 bioisostere warrants further development.