Synthesis of new 4-aminoquinolines and quinoline-acridine hybrids as antimalarial agents.
Despite emergence of resistance to CQ and other 4-aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-aminoquinoline antimalarials. In present study, new side chain modified 4-aminoquinoline derivatives and quinoline-acridine hybrids were synthesized and evaluated in vitro against NF 54 strain of Plasmodium falciparum. Among the evaluated compounds, compound 17 (MIC=0.125 μg/mL) was equipotent to standard drug CQ (MIC=0.125 μg/mL) and compound 21 (MIC=0.031 μg/mL) was four times more potent than CQ. Compound 17 showed the curative response to all the treated swiss mice infected with CQ-resistant N-67 strain of Plasmodium yoelii at the doses 50 mg/kg and 25 mg/kg for four days by intraperitoneal route and was found to be orally active at the dose of 100 mg/kg for four days. The promising antimalarial potency of compound 17 highlights the significance of exploring the privileged 4-aminoquinoline class for new antimalarials.
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow, India.
Ashok
A
Kumar
Kumkum
K
Srivastava
S Raja
SR
Kumar
S K
SK
Puri
Prem M S
PM
Chauhan
D000166:Acridines / Q000737:chemistry* / Q000493:pharmacokinetics; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D051379:Mice; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
D000166:Acridines; D000634:Aminoquinolines; D000962:Antimalarials; D011804:Quinolines; C001920:4-aminoquinoline