1.Institute of Chemical Biology,Henan University,Kaifeng 475001,China; 2.Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
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--oxadiazol- 2-methylsulfanyl)-4H--triazol-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)were 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.
XU Qiu-Ju-,
HOU Li-Li-,
WU Zhao-Feng- etc
.Synthesis and Antitumor Evaluation of Fluoroquinolon C3 s-Triazole Oxadiazole Methylsulfide Derivatives of Ofloxacin[J] Chinese Pharmaceutical Journal, 2014,V49(7): 609-612
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