In vitro anti-malarial efficacy of chalcones: cytotoxicity profile, mechanism of action and their effect on erythrocytes
| Autor: | Ashish Bhalla, Bikash Medhi, Shweta Sinha, Bishan Dass Radotra, Rakesh Sehgal, Nadezhda Markova, Daniela I. Batovska |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Hemeproteins Chalcone lcsh:Arctic medicine. Tropical medicine Erythrocytes lcsh:RC955-962 Cell Survival Plasmodium falciparum Pharmacology 01 natural sciences Hemolysis lcsh:Infectious and parasitic diseases Haemozoin 03 medical and health sciences chemistry.chemical_compound Antimalarials Inhibitory Concentration 50 Chalcones In vitro Chloroquine parasitic diseases Drug Discovery medicine Humans lcsh:RC109-216 Viability assay Cytotoxicity Mode of action biology 010405 organic chemistry Chemistry Research Plants biology.organism_classification Haemolysis 0104 chemical sciences Malaria 030104 developmental biology Infectious Diseases Mechanism of action Parasitology medicine.symptom medicine.drug HeLa Cells |
| Zdroj: | Malaria Journal Malaria Journal, Vol 18, Iss 1, Pp 1-11 (2019) |
| ISSN: | 1475-2875 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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