ABSTRACT
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.
Subject(s)
Aminoquinolines/therapeutic use , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Amides , Aminoquinolines/chemical synthesis , Aminoquinolines/pharmacology , Animals , Anti-Bacterial Agents , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Parasitemia , Plasmodium falciparum/drug effects , Treatment OutcomeABSTRACT
Synthesis of new 6-ureido-4-anilinoquinazolines have been accomplished and their in vitro antimalarial activity against chloroquine-sensitive P. falciparum have been examined. Out of 64 compounds evaluated, the IC(50) of 16 compounds which have displayed MIC of 0.25 microg/mL were also recorded. One of the compounds (24 g) had IC(50) value of 2.27 ng/mL which was equipotent to the standard drug chloroquine used in the bioassay. The in vivo evaluation of a few compounds among the series led to discovery of one analog (30 g) displaying 40% curative activity (28 days) against mdr P. yoeillinigeriensis at an oral dose of 100 mg/kg x 4 days.
