title: Synthesis and bioevaluation of novel 4-aminoquinoline-tetrazole derivatives as potent antimalarial agents.
abstract: A series of novel tetrazole derivatives of 4-aminoquinoline were synthesized and screened for their antimalarial activities against both chloroquine-senstive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum as well as for cytotoxicity against VERO cell lines. Most of the synthesized compounds exhibited potent antimalarial activity as compared to chloroquine against K1-strain. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii following both intraperitoneal (ip) and oral administration, wherein compounds 20 and 23 each showed in vivo suppression of 99.99% parasitaemia on day 4.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Pandey
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.forename: S
authors.initials: S
authors.lastname: Rajakumar
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.forename: Pravesh
authors.initials: P
authors.lastname: Verma
authors.forename: J K
authors.initials: JK
authors.lastname: Saxena
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
authors.forename: Prem M S
authors.initials: PM
authors.lastname: Chauhan
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D006420:Hemeproteins / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013777:Tetrazoles / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; D013777:Tetrazoles; C045574:1H-tetrazole; C020753:hemozoin; C001920:4-aminoquinoline
keywords: 4-Aminoquinoline; Antimalarial; Chloroquine; Cytotoxicity; Tetrazole