Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. (December 2017)

• Record Type: Journal Article
• Authors: Yeo, Seon-Ju; Liu, Dong-Xu; Kim, Hak; Park, Hyun
• Is Part Of: Malaria journal. Volume 16:Number 1(2017)
• Page Start: 1
• Page End: 9
• Publication Date: 2017-12
• Subjects: Chloroquine derivatives -- SKM13 -- Anti-malarial efficacy -- α, β-unsaturated amides; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-017-1725-z
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Background 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. Results 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 strainPlasmodium falciparum . An in vivo mouse study demonstrated that SKM13 (20 mg/kg) could completely inhibitPlasmodium 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 inP. berghei -infected mice over 12 days, but the SKM13 (20 mg/kg)-treated group showed no loss of RBC. Conclusions CQ derivatives with substituents such as α, β-unsaturated amides and phenylmethyl group have enhanced anti-malarial activity against the CQ-resistant strainP. falciparum, and SKM13 is an excellent anti-malarial drug candidate in mice model.