Publication: Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents
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Issued Date
2014-10-06
Resource Type
ISSN
17683254
02235234
02235234
Other identifier(s)
2-s2.0-84905161366
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Mahidol University
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SCOPUS
Bibliographic Citation
European Journal of Medicinal Chemistry. Vol.85, (2014), 65-76
Suggested Citation
Ratchanok Pingaew, Amporn Saekee, Prasit Mandi, Chanin Nantasenamat, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents. European Journal of Medicinal Chemistry. Vol.85, (2014), 65-76. doi:10.1016/j.ejmech.2014.07.087 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/33614
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Title
Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents
Abstract
A new series of chalcone-coumarin derivatives (9-19) linked by the 1,2,3-triazole ring were synthesized through the azide/alkyne dipolar cycloaddition. Hybrid molecules were evaluated for their cytotoxic activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) and antimalarial activity toward Plasmodium falciparum. Most of the synthesized hybrids, except for analogs 10 and 16, displayed cytotoxicity against MOLT-3 cell line without affecting normal cells. Analogs (10, 11, 16 and 18) exhibited higher inhibitory efficacy than the control drug, etoposide, in HepG2 cells. Significantly, the high cytotoxic potency of the hybrid 11 was shown to be non-toxic to normal cells. Interestingly, the chalcone-coumarin 18 was the most potent antimalarial compound affording IC50value of 1.60 μM. Molecular docking suggested that the cytotoxicity of reported hybrids could be possibly due to their dual inhibition of α- and β-tubulins at GTP and colchicine binding sites, respectively. Furthermore, falcipain-2 was identified to be a plausible target site of the hybrids given their antimalarial potency. © 2014 Elsevier Masson SAS. All rights reserved.