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

Aktaş D., Akinalp G., Sanli F., Yucel M. A., Gambacorta N., Nicolotti O., ...Daha Fazla

Bioorganic and Medicinal Chemistry Letters, cilt.30, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.bmcl.2020.127427
  • Dergi Adı: Bioorganic and Medicinal Chemistry Letters
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Synthesis, Isoxazole, Anticancer agent, Molecular modeling, Proliferation, PROSTATE-CANCER, CYTOCHROME-P450 1B1, SUPPRESSION, INHIBITION, EXPRESSION, APOPTOSIS
  • Atatürk Üniversitesi Adresli: Evet

Özet

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, H-1 NMR, C-13 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.