Search for new pharmacophores for antimalarial activity. Part I: synthesis and antimalarial activity of new 2-methyl-6-ureido-4-quinolinamides.
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.
Madapa
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S
Medicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow, UP 226001, India.
Tusi
Z
Z
Sridhar
D
D
Kumar
A
A
Siddiqi
M I
MI
Srivastava
K
K
Rizvi
A
A
Tripathi
R
R
Puri
S K
SK
Shiva Keshava
G B
GB
Shukla
P K
PK
Batra
S
S
D000577:Amides; D000634:Aminoquinolines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects; D016896:Treatment Outcome
D000577:Amides; D000634:Aminoquinolines; D000900:Anti-Bacterial Agents; D000962:Antimalarials