Abstract
BackgroundDespite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection. Haemozoin is considered as a novel inhibitory pathway for new anti-malarial drugs, therefore, this study aimed to systematically review all articles investigating the correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds.MethodsA literature search was conducted on 22 October 2017 in eight databases for relevant in vitro articles reporting the correlation between anti-malarial and anti-haemozoin of anti-malarial compounds, based on the constructed search terms and inclusion criteria. ToxRtool was used to assess quality of each study.ResultsA total of ten articles were included in the review. In vitro anti-malarial and anti-haemozoin activity had a good correlation for quinolines for sensitive strains (R2 ranging from 0.66 to 0.95) and xanthones (Spearman ρ = 0.886). However, these correlations were reached after removing some compounds which had non-detectable anti-malarial or anti-haemozoin effects. Other structures (acridines, pyrolidines) showed negligible correlation with Spearman ρ ranging from 0.095 to 0.381 for acridines, and r varying from 0.54 to 0.62 for pyrolidines. Some good correlations were only shown in a logarithmic manner or when the anti-malarial activity was normalized.ConclusionThe results raised a relative relationship between anti-haemozoin and in vitro anti-malarial activities. Some studies reported compounds that were effective in the inhibition of haemozoin formation, but failed to inhibit the parasite survival and vice versa. The correlation results in these studies were calculated after these compounds were removed from their analysis. The ability of anti-malarial compounds to accumulate inside the reaction site might strengthen their anti-malarial activity.
Highlights
Despite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection
To have a thorough perspective relating to the probable efficacy of anti-haemozoin compounds so that more antimalarial candidates could be screened, this study aimed to investigate the correlation between anti-malarial and anti-haemozoin activity by conducting a systematic review
The results reported by Kaschula et al [32] showed the evidence relating to the role of pH trapping to the correlation between in vitro anti-malarial and antihaemozoin activities, as the correlation between these activities was only observed when IC50 values were normalized by multiplying with the vacuolar accumulation
Summary
Despite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection. Chloroquine (CQ) has been an anti-malarial agent since 1940s as an efficient treatment with a wide safety margin and lower reported side effects [5]. It has been replaced by artemisinin-based combination therapy (ACT) as a widely used anti-malarial treatment. Signs of resistance to artemisinin-based combinations have been reported leading to the need of new anti-malarial agents fighting malaria infection [6, 7]. That can be resulted from the misuse of anti-malarial drugs for the benefit of prophylaxis, monotherapy usage, and the reduced application of effective therapy for malarial patients [1, 8,9,10,11,12,13,14]
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