A series of 30 compounds were synthetized inspired by active trans-fagaramide structure skeleton. On this synthetic platform, 18 compounds were achieved via Knoevenagel condensation using maleic acid and piperonal, followed by peptide coupling with various amines, giving an average yield of 54%. Subsequently, nine compounds were obtained by palladium-mediated Heck coupling with an average yield of 79%. In addition, cytotoxic activity was evaluated against cardiomyoblast H9c2, breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2, and glioblastoma U-87 cells. The results revealed two aryl halogen-substituted compounds moderately active against H9c2 and MCF7 with IC50 values > 50 μM. One functionalized coumarin showed inhibitory activity against H9c2 (IC50 > 50 μM). In contrast, p-aminophenyl-β-monosubstituted trans-fagaramide was found to inhibit MCF7 (IC50 > 50 μM) without showing toxicity against H9c2 cells.
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M. Barrera did all the synthesis as a part of her Master Thesis and wrote the paper. T. C. Shiao contributed to the interpretation of spectra. P. T. Nguyen and S. Bourgault performed evaluation of the cytotoxic activity. R. Roy designed thematics and supervised all experiments presented in the paper.
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Tomas, M.B., Shiao, T.C., Nguyen, P.T. et al. Synthesis of Analogs of Trans-Fagaramide and Their Cytotoxic Activity. Pharm Chem J 51, 995–1004 (2018). https://doi.org/10.1007/s11094-018-1729-1
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DOI: https://doi.org/10.1007/s11094-018-1729-1