Synthesis and Antitumor Activity of Fluoroquinolone C-3 Fused Heterocyclic Thiazolo[3,2-b][1,2,4]triazole Derivatives(��)
WU Shu-min1, YAN Qiang1, NI Li-li1, XIE Yu-suo1, GAO Liu-zhou1, LIU Ying-jie3*, HUANG Wen-long2, HU Guo-qiang1*
1.Institute of Chemical Biology, Henan University, Kaifeng 475001, China; 2. Centre of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China; 3.Department of Microbiology, Medical College Henan University, Kaifeng 475001, China
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-b][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.
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2016, Vol. 51 
