4-Aminoquinoline derived antimalarials: synthesis, antiplasmodial activity and heme polymerization inhibition studies.
A new series of 4-aminoquinoline derivatives have been synthesized and found to be active against both susceptible and resistant strains of Plasmodium falciparum in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl-thiourea (7) exhibited superior in vitro activity against resistant strains of P. falciparum as compared to chloroquine (CQ). All the compounds showed resistance factor between 0.59 and 4.31 as against 5.05 for CQ. Spectroscopic studies suggested that this class of compounds act on heme polymerization target.
Solomon
V R
VR
Medicinal and Process Chemistry Division, Central Drug Research Institute, MG Road, Lucknow 226 001, India.
Haq
W
W
Smilkstein
M
M
Srivastava
Kumkum
K
Puri
Sunil K
SK
Katti
S B
SB
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000634:Aminoquinolines; D000962:Antimalarials; D011108:Polymers; D006418:Heme; C001920:4-aminoquinoline