8-Quinolinamines conjugated with amino acids are exhibiting potent blood-schizontocidal antimalarial activities.
Alanine, lysine, ornithine and valine conjugated to primaquine and other 8-quinolinamine antimalarials were prepared for blood-schizontocidal antimalarial activity evaluation. The analogues were examined in vivo against Plasmodium berghei (drug-sensitive strain) and Plasmodium yoelii nigeriensis (highly virulent multi-drug-resistant strain) infected mice models. N(1)-[4-(5-Butoxy-4-ethyl-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (20) which showed curative activity at 5mg/kg in the P. berghei test emerged as the most effective compound. N(1)-[4-(4-Ethyl-5-hexoxy-6-methoxy-8-quinolylamino)pentyl]-(2S)-2,6-diaminohexanamide (22) exhibited curative activity at 50mg/kg against P. yoelii nigeriensis in mice and emerged as the most potent analogue against multi-drug resistant strain. The results of this study represent development of highly potent 8-quinolinamines for antimalarial drug development.
Vangapandu
Suryanarayana
S
National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160 062, India.
Sachdeva
Sandeep
S
Jain
Meenakshi
M
Singh
Savita
S
Singh
Prati Pal
PP
Kaul
Chaman Lal
CL
Jain
Rahul
R
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D008288:Malaria / Q000097:blood* / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects / Q000254:growth & development; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development
D000596:Amino Acids; D000634:Aminoquinolines; D000962:Antimalarials; C080436:8-aminoquinoline