title: Antimalarial activity of novel 4-aminoquinolines active against drug resistant strains.
abstract: In the present study we have synthesized a new class of 4-aminoquinolines and evaluated against Plasmodium falciparum in vitro (3D7-sensitive strain & K1-resistant strain) and Plasmodium yoelii in vivo (N-67 strain). Among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against K1 strain as compared to CQ. In addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against N-67 strain when administered orally. Further, biophysical studies suggest that this series of compounds act on heme polymerization target.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Kondaparla
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Awakash
authors.initials: A
authors.lastname: Soni
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Ashan
authors.initials: A
authors.lastname: Manhas
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: setu_katti@yahoo.com.
authors.forename: S B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D055808:Drug Discovery; D004351:Drug Resistance; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C001920:4-aminoquinoline
keywords: 4-Aminoquinoline; Antimalarial; Heam binding; Plasmodium falciparum