Synthesis, in vitro antitrypanosomal and antibacterial activity of phenoxy, phenylthio or benzyloxy substituted quinolones.
Chagas' disease, caused by Trypanosoma cruzi(T. cruzi), is one of the most serious parasitic diseases in Latin America. The currently available chemotherapy, based on nifurtimox or benznidazole, is unsatisfactory due to the limited efficacy in the prevalent chronic stage of the disease and toxic side effects. In order to address these deficiencies, a series of quinolones based novel molecules have been synthesized and evaluated as potential antitrypanosomal agents. The most active analogue 10 inhibited T. cruzi with an IC(50) of 1.3 microg/mL. The results of this study have implications in the development of novel quinolone's antitrypanosomal agents.
Ma
Xiang
X
State Key Lab of New Drug & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan Road, Shanghai 200437, PR China. chemx@nus.edu.sg
Zhou
Weicheng
W
Brun
Reto
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D014355:Chagas Disease / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009593:Nitroimidazoles / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D015363:Quinolones; D014344:Trypanocidal Agents; C009999:benzonidazole