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- Title
In vitro anti-malarial efficacy of chalcones: cytotoxicity profile, mechanism of action and their effect on erythrocytes.
- Authors
Sinha, Shweta; Batovska, Daniela I.; Medhi, Bikash; Radotra, B. D.; Bhalla, Ashish; Markova, Nadezhda; Sehgal, Rakesh
- Abstract
Background: Malaria extensively leads to mortality and morbidity in endemic regions, and the emergence of drug resistant parasites is alarming. Plant derived synthetic pharmaceutical compounds are found to be a foremost research to obtain diverse range of potent leads. Amongst them, the chalcone scaffold is a functional template for drug discovery. The present study involves synthesis of ten chalcones with various substitution pattern in rings A and B and assessment of their anti-malarial efficacy against chloroquine sensitive and chloroquine resistant strains as well as of their cytotoxicity and effect on haemozoin production. Methods: The chalcones were synthesized by Claisen-Schmidt condensation between equimolar quantities of substituted acetophenones and aryl benzaldehydes (or indole-3-carboxaldehyde) and were screened for anti-malarial activity by WHO Mark III schizont maturation inhibition assay. The cytotoxicity profile of a HeLa cell line was evaluated through MTT viability assay and the selectivity index (SI) was calculated. Haemozoin inhibition assay was performed to illustrate mode of action on a Plasmodium falciparum strain. Results: The IC50 values of all compounds were in the range 0.10–0.40 μg/mL for MRC-2 (a chloroquine sensitive strain) and 0.14–0.55 μg/mL for RKL-9 (a chloroquine resistant strain) of P. falciparum. All the chalcones showed low cellular toxicity with minimal haemolysis. The statistically significant reduction (p < 0.05) in the haemozoin production suggests a similar mechanism than that of chloroquine. Conclusions: Out of ten chalcones, number 7 was found to be a lead compound with the highest potency (IC50 = 0.11 µg/mL), as compared to licochalcone (IC50 = 1.43 µg/mL) and with high selectivity index of 85.05.
- Subjects
BIOCHEMICAL mechanism of action; CHALCONES; DOSAGE forms of drugs; ACETOPHENONE; HELA cells
- Publication
Malaria Journal, 2019, Vol 18, Issue 1, p1
- ISSN
1475-2875
- Publication type
Article
- DOI
10.1186/s12936-019-3060-z