Evaluation of Cytotoxic Profile of Some Chalcone Derivatives with Antimalarial Properties
Chemical Science International Journal,
Malaria continues to kill thousands of people worldwide. People South of the Sahara are paying the heaviest price for this epidemic. In addition, the resistance of Plasmodium falciparum which spreads to artemisinin derivatives becomes worrying. To respond to this emergency, the search for new molecules effective against the parasite is essential. Otherwise, chalcones have shown their potential as an effective pharmaceutical agent in numerous studies. However, despite their mainly antiparasitic efficacy, several compounds have been shown to be cytotoxic. This study aimed to assess the cytotoxic profile of chalcone derivatives. Cytotoxicity tests were carried out according to the method described by Taylor and collaborators on Vero cells. The 96-well plates were used in carrying out this study, 100 µl of the compounds were added with concentrations ranging from 7.5 to 1000 µg/ml in DMEM. The results obtained report three compounds derivatives (Chal_B14, Chal_B17 & Chal_SCA03) no-cytotoxic with LDH product values between 129 - 132.5 U/L and ATP ranging from 8.55 to 13.6 RLU. The IC50s for no-cytotoxic compounds ranged from 102 to 236 µM. On the other hand, the cytotoxic compounds had IC50s of less than 30 µM.
The results of this study show that the derivatives Chal_B14, Chal_B17 & Chal_SCA03 are candidate compounds with a view to finding new molecules.
- Cell cytoxicity
- Plasmodium falciparum
- vero cells
- chalcone derivatives.
How to Cite
Lu F, Culleton R, Zhang M, Ramaprasad A, von Seidlein L, Zhou H, et al. Emergence of Indigenous Artemisinin-Resistant Plasmodium falciparum in Africa. New England Journal of Medicine. 2017; 1-3.
Sinha S, Medhi B, Sehgal R. Chalcones as an emerging lead molecule for antimalaria therapy: A review. Journal of Modern Medicinal Chemistry. 2013;1(2):64- 77.
Asif M. A review on recent advances and potential pharmacological activities of versatile chalchone molecule. Chemistry International. 2016;2(1):1-18.
Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: Old and new aspects of aclass of natural therapeutic drugs. Life Sciences. 1999;65(4):17.
Dimmock JR, Elias DWMB, Kandepu N. Bioactives chalcones. Curr Med Chem. 1999;6(12):1-25.
Awasthi SK, Nidhi M, Brajesh K, Manish S, Amit B, Mishra LC, et al. Potent antimalarial activity of newly synthesized substituted chalcone analogs in vitro. Medicinal Chemistry Research. 2009;18 (6):407-420.
Chen M, Theander TG, Christensen SB, Hviid L, Zhai L, Kharazemi A. Licochalcone A. A new antimalarial agent, inhibits in vitro growth of the human malaria Parasite Plasmodium falciparum and protects mice from P yoelli infection. Antimicrobial Agents and Chemotherapy. 1994;38(7): 1470-1475.
Lee YT, Fong TH, Chen HM, Chang CY, Wang YH, Chern CY, et al. Toxicity assessments of chalcone and some synthetic chalcone analogues in a Zebrafish model. Molecules. 2014;19:641-650.
Kretzmer G. Industrial processes with animal cells. Applied Microbiology and Biotechnology. 2002;59(2):1-8.
Wu J, Wang C, Cai Y, Peng J, Liang D, Zhao Y, et al. Synthesis and crystal structure of chalcones as well as on cytotoxicity and antibacterial properties. Med Chem Res. 2012;21:444-452.
Dable MT, Tano KD, Ouattara M, Silue KD, Menan EIH, Yavo W. Ex vivo efficacy of selective chalcone derivatives on reference strains and field isolates of Plasmodiumfalciparum. Pathog Glob Health. 2019;113(8):359-363.
Fasinu PS, Tekwani BL, Avula B, Chaurasiya ND, Nanayakkara NPD, Wang YH, et al. Pathway-specific inhibition of primaquine metabolism by chloroquine/ quinine. Malaria Journal. 2016;15(466):1-12.
Riveron JM, Chiumia M, Mnze BD, Barnes KG, Irving H, Ibrahim SS, et al. Rise of multiple insecticide resistance in Anopheles funestus in Malawi: a major concern for malaria vector control. Malaria Journal. 2015;14(344):1-9.
Sun XY, Ouyang JM, Wen Yu Zhu, Liab YB, Gana QZ. Size-dependent toxicity and interactions of calcium oxalate dihydrate crystals on Vero renal epithelial cells. Journal of Materials Chemistry B. 2015;3: 1864-1878.
Crouch SPM, Kozlowski R, Slater KJ, Fletcher J. The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity. Journal of Immunological Methods. 1993;160:81-88.
Hannah R, Beck M, Moravec R, and Riss T. Celltiter-glo™ luminescent cellviability assay: A sensitive and rapid method for determining cellviability. Cell Notes. 2001(2):1-3.
Kwak S-Y, Jeong YJ, Park JS, JHC. Bio-LDH nanohybrid for gene therapy. Solid State Ionics. 2002;151:229-234.
Schulze-Osthoff K, Bakkerg A. C, Vanhaesebroeck B, Beyaert R, Jacob W. A, Fiers W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. The Journal of Biological Chemistry. 1992;267 (6):5317-5323.
Chong MWK, Gu KD, Lam PKS, Yang M, and Fong WF. Study on the cytotoxicity of microcystin-LR on cultured cells. Chemosphere. 2000;41:143-147.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol Methods. 1983;65:55-63.
Pradines B, Tall A, Rogier C, Spiegel A, Mosnier J, Marrama L, et al. In vitro activities of ferrochloroquine against 55 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Tropical Medicine and International Health. 2002;7 (3):265-270.
Xia M, Huang R, Witt KL, Southall N, Fostel J, Cho MH, et al. Compound cytotoxicity profiling using quantitative high-throughput screening. Environmental Health Perspectives. 2008;116(3):284-291.
Harveer Singh Cheema, Om Prakash, Anirban Pala, Feroz Khan, Dnyneshwar U. Bawankule, Mahendra P. Darokar. Glabridin induces oxidative stress mediated apoptosis like cell death of malaria parasite Plasmodium falciparum. Elsevier. 2014;63(2):349-358.
Sriphana U, Yenjai C, Tungnoi S, Srirapa J, Junsongduang A. Flavonoids from Milletia leucantha and their cytotoxicity. Natural Product Communications. 2018;13 (8):961-962.
Rizvi S. U. F, Siddiqui H. L, Johns M, Detorio M, and Schinazi R F. Anti-HIV-1 and cytotoxicity studies of piperidyl-thienyl chalcones and their 2-pyrazoline derivatives. Med Chem Res. 2012;21: 3741-3749.
Pande AN, Biswas S, Reddy ND, Jayashree BS, Kumar N, Rao CM. In vitro and in vivo anticancer studies of 2′-hydroxy chalcone derivatives exhibit apoptosis in colon cancer cells by hdac inhibition andcell cycle arrest. EXCLI Journal. 2017;16:448- 463.
Bahuguna A, Khan I, Bajpai VK, Kang SC. MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh J Pharmacol. 2017;12:115-118.
Aponte JC, MV, Malaga E, Zimic M, Quiliano M, Vaisberg A. J, et al. Synthesis, Cytotoxicity, and Anti-Trypanosoma cruzi Activity of New Chalcones. J Med Chem. 2008;51(19): 6230-6234.
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