title: Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria.
abstract: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity.
  
  
  
  Novel two derivatives (SKM13 and SKM14) were synthesized based on the chloroquine (CQ) template containing modified side chains such as α,β-unsaturated amides and phenylmethyl group. The selective index indicated that SKM13 was 1.28-fold more effective than CQ against the CQ-resistant strain Plasmodium falciparum. An in vivo mouse study demonstrated that SKM13 (20 mg/kg) could completely inhibit Plasmodium berghei growth in blood and increased the survival rate from 40 to 100% at 12 days after infection. Haematological parameters [red blood cell (RBC) count, haemoglobin level, and haematocrit level] were observed as an indication of clinical malarial anaemia during an evaluation of the efficacy of SKM13 in a 4-day suppression test. An in vivo study showed a decrease of greater than 70% in the number of RBC in P. berghei-infected mice over 12 days, but the SKM13 (20 mg/kg)-treated group showed no loss of RBC.
  
  
  
  CQ derivatives with substituents such as α,β-unsaturated amides and phenylmethyl group have enhanced anti-malarial activity against the CQ-resistant strain P. falciparum, and SKM13 is an excellent anti-malarial drug candidate in mice model.
authors.affiliation: Department of Infection Biology, School of Medicine, Zoonosis Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeolabuk-do, 54538, Republic of Korea.
authors.forename: Seon-Ju
authors.initials: SJ
authors.lastname: Yeo
authors.affiliation: Department of Infection Biology, School of Medicine, Zoonosis Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeolabuk-do, 54538, Republic of Korea.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University, 460, Iksan-daero, Iksan, Jeolabuk-do, 54538, Republic of Korea. hankidad@wku.ac.kr.
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Infection Biology, School of Medicine, Zoonosis Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeolabuk-do, 54538, Republic of Korea. hyunpk@wku.ac.kr.
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008288:Malaria / Q000097:blood / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D002738:Chloroquine
keywords: Anti-malarial efficacy; Chloroquine derivatives; SKM13; α,β-unsaturated amides