Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents

Bioorg Med Chem Lett. 2020 Oct 1;30(19):127427. doi: 10.1016/j.bmcl.2020.127427. Epub 2020 Jul 23.

Abstract

The present study was carried out in the attempt to synthesize a new class of potential anticancer agents comprising eleven compounds (24-34) sharing the 3,5-diarylisoxazole as a core. The chemical structure of the new synthesized compounds was established by IR, 1H NMR, 13C NMR and elemental analysis. Their biological potential towards prostate cancer was evaluated by using cancer PC3 cells and non-tumorigenic PNT1a cells. Interestingly, compound 26 distinguished from others with a quite high selectivity value that is comparable to 5-FU. The binding mode of 26 towards Ribosomal protein S6 kinase beta-1 (S6K1) was investigated at a molecular level of detail by employing docking simulations based on GLIDE standard precision as well as MM-GBSA calculations.

Keywords: Anticancer agent; Isoxazole; Molecular modeling; Proliferation; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Isoxazoles / chemical synthesis
  • Isoxazoles / metabolism
  • Isoxazoles / pharmacology*
  • Molecular Docking Simulation
  • PC-3 Cells
  • Protein Binding
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism

Substances

  • Antineoplastic Agents
  • Isoxazoles
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1