Silalai Patamawadee, Pruksakorn Dumnoensun, Chairoungdua Arthit, Suksen Kanoknetr, Saeeng Rungnapha
Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
Musculoskeletal Science and Translational Research Center, Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Omics Center for Health Sciences, Faculty of Medicine, Chiang Mai University, Thailand.
Bioorg Med Chem Lett. 2021 Aug 1;45:128135. doi: 10.1016/j.bmcl.2021.128135. Epub 2021 May 24.
Twenty six propargylamine mycophenolate analogues were designed and synthesized from mycophenolic acid 1 employing a key step A-coupling reaction. Their cytotoxic activity was examined against six cancer cell lines. Compounds 6a, 6j, 6t, 6u, and 6z exhibited selective cytotoxicity towards neuroblastoma (SH-SY5Y) cancer cells and were less toxic to normal cells in comparison to the lead compound, MPA 1 and a standard drug, ellipticine. Molecular docking results suggested that compound 6a is fit well in the key amino acid of three proteins (CDK9, EGFR, and VEGFR-2) as targets in cancer therapy. The propargylamine mycophenolate scaffold might be a valuable starting point for development of new neuroblastoma anticancer drugs.
从霉酚酸1出发，通过关键步骤A-偶联反应设计并合成了26种炔丙胺霉酚酸类似物。检测了它们对六种癌细胞系的细胞毒性活性。化合物6a、6j、6t、6u和6z对神经母细胞瘤（SH-SY5Y）癌细胞表现出选择性细胞毒性，与先导化合物霉酚酸1和标准药物玫瑰树碱相比，对正常细胞的毒性较小。分子对接结果表明，化合物6a与作为癌症治疗靶点的三种蛋白质（CDK9、EGFR和VEGFR-2）的关键氨基酸契合良好。炔丙胺霉酚酸支架可能是开发新型神经母细胞瘤抗癌药物的有价值的起始点。
