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 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.
authors: Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. Electronic address: ratchanok@swu.ac.th.
authors: Ratchanok
authors: R
authors: Pingaew
authors: Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
authors: Amporn
authors: A
authors: Saekee
authors: 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.
authors: Prasit
authors: P
authors: Mandi
authors: 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.
authors: Chanin
authors: C
authors: Nantasenamat
authors: Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
authors: Supaluk
authors: S
authors: Prachayasittikul
authors: 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.
authors: Somsak
authors: S
authors: Ruchirawat
authors: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
authors: Virapong
authors: V
authors: Prachayasittikul
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003374:Coumarins / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects; D011487:Protein Conformation; D014230:Triazoles / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D003374:Coumarins; D014230:Triazoles; D014404:Tubulin; D002599:Chalcone; C030123:coumarin; D003546:Cysteine Endopeptidases; C416224:falcipain 2
keywords: Antimalarial activity; Chalcone; Coumarin; Cytotoxicity; Molecular docking; Triazole