Madapa S, Tusi Z, Sridhar D, Kumar A, Siddiqi M I, Srivastava K, Rizvi A, Tripathi R, Puri S K, Shiva Keshava G B, Shukla P K, Batra S
Medicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow, UP 226001, India.
Bioorg Med Chem. 2009 Jan 1;17(1):203-21. doi: 10.1016/j.bmc.2008.11.021. Epub 2008 Nov 18.
A total of 80 new 2-methyl-6-ureido-4-quinolinamides were synthesized and evaluated for their antimalarial activity. Several analogs elicited the antimalarial effect at MIC of 0.25 mg/mL against the chlooquine-sensitive P. falciparum strain. The IC(50) values of the active compounds were observed to be in ng/mL range and two of the analogs have better IC(50) value than the standard chloroquine. In the in vivo assay against mdr CQ resistant P. yoelii N67/P. yoelii nigeriensis, however, none of the compound showed complete suppression of parasitemia on day 7. One of the compounds displayed significant antibacterial effect against several strains of bacteria and was many-fold better than the standard drug gentamicin.
共合成了80种新型2-甲基-6-脲基-4-喹啉酰胺，并对其抗疟活性进行了评估。几种类似物对氯喹敏感的恶性疟原虫菌株在0.25 mg/mL的最低抑菌浓度下产生了抗疟效果。活性化合物的半数抑制浓度（IC50）值在纳克/毫升范围内，其中两种类似物的IC50值比标准氯喹更好。然而，在针对耐多药氯喹的约氏疟原虫N67/约氏疟原虫尼日尔株的体内试验中，第7天没有一种化合物显示出对疟原虫血症的完全抑制。其中一种化合物对几种细菌菌株显示出显著的抗菌作用，且比标准药物庆大霉素好很多倍。
