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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[1]
HUBBINS D J,SHERMAN W,TIDER B. Rational approaches to improving selectivity in drug design. J Med Chem,2012,55(4):1424-1444. [2] HAMADA Y,KISO Y. The application of bioisosteres in drug design for novel drug discovery:Focusing on acid protease inhibitors. Exper Opin Drug Discov,2012,7(10):903-922. [3] BAX B D,CHAN P F,EGGLESTON D S,et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature,2010,466(7309):935-940. [4] HU G Q,CHEN Y S,WANG G Q,et al. Synthesis of fluoroquinolone C-3 heterocycles,bis-oxadiazole methylsulfides and methiodide,and their antitumor activity. Chin Pharm J(�й�ҩѧ��־),2012,47(1):72-76. [5] HU G Q,XIE S Q,XU Q J,et al. Synthesis and antibacterial activity of 3-(5-substituted phenyl-oxadiazole-2-yl-methylenethio)-5-pyridin-3-yl--triazole-4-yl-amines]. Acta Pharm Sin(ҩѧѧ��),2005,40(4):337-339.
2014, Vol. 49 
