2. Academic Validation
  3. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents

Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents

  • Eur J Med Chem. 2014 Oct 6:85:65-76. doi: 10.1016/j.ejmech.2014.07.087.
Ratchanok Pingaew 1,  Amporn Saekee 2,  Prasit Mandi 3,  Chanin Nantasenamat 3,  Supaluk Prachayasittikul 4,  Somsak Ruchirawat 5,  Virapong Prachayasittikul 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. Electronic address: ratchanok@swu.ac.th.
  • 2 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
  • 3 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 4 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 5 Chulabhorn Research Institute, Bangkok 10210, Thailand; Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Thailand.
  • 6 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
PMID: 25078311 DOI: 10.1016/j.ejmech.2014.07.087
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 IC50 value 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.

Keywords

Antimalarial activity; Chalcone; Coumarin; Cytotoxicity; Molecular docking; Triazole.

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