title: Synthesis of chiral chloroquine and its analogues as antimalarial agents.
abstract: In this investigation, we describe a new approach to chiral synthesis of chloroquine and its analogues. All tested compounds displayed potent activity against chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum in vitro and Plasmodium yoelii in vivo. Compounds S-13 b, S-13c, S-13 d and S-13 i displayed excellent in vitro antimalarial activity with an IC50 value of 56.82, 60.41, 21.82 and 7.94 nM, respectively, in the case of resistant strain. Furthermore, compounds S-13a, S-13c and S-13 d showed in vivo suppression of 100% parasitaemia on day 4 in the mouse model against Plasmodium yoelii when administered orally. These results underscore the application of synthetic methodology and need for further lead optimization.
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Sinha
authors.affiliation: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Vasanth R
authors.initials: VR
authors.lastname: Dola
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: Pooja
authors.initials: P
authors.lastname: Agarwal
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: Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Wahajul
authors.initials: W
authors.lastname: Haq
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: Seturam B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D002738:Chloroquine; C001920:4-aminoquinoline
keywords: 4-Aminoquinolines; Chiral chloroquine analogues; Chloroquine resistant stain