2. Academic Validation
  3. Synthesis of propargylamine mycophenolate analogues and their selective cytotoxic activity towards neuroblastoma SH-SY5Y cell line

Synthesis of propargylamine mycophenolate analogues and their selective cytotoxic activity towards neuroblastoma SH-SY5Y cell line

  • Bioorg Med Chem Lett. 2021 Aug 1:45:128135. doi: 10.1016/j.bmcl.2021.128135.
Patamawadee Silalai 1,  Dumnoensun Pruksakorn 2,  Arthit Chairoungdua 3,  Kanoknetr Suksen 3,  Rungnapha Saeeng 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
  • 2 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.
  • 3 Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
  • 4 Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand; The Research Unit in Synthetic Compounds and Synthetic Analogues from Natural Product for Drug Discovery (RSND), Burapha University, Chonburi 20131, Thailand. Electronic address: rungnaph@buu.ac.th.
PMID: 34044119 DOI: 10.1016/j.bmcl.2021.128135
Abstract

Twenty six propargylamine mycophenolate analogues were designed and synthesized from mycophenolic acid 1 employing a key step A3-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.

Keywords

A(3)-coupling reaction; Cytotoxic activity; Molecular docking; Mycophenolic Acid; Neuroblastoma SH-SY5Y cells; Propargylamine mycophenolate.

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