Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents
Bioorganic and Medicinal Chemistry Letters, cilt.30, 2020 (SCI-Expanded, Scopus)
- 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.