Novel Schiff Bases: Synthesis, Characterization, Bioactivity, Cytotoxicity, and Computational Evaluations


Medetalibeyoğlu H., Manap S., Alkan M., Beytur M., Barlak N., Karatas O. F., ...Daha Fazla

Polycyclic Aromatic Compounds, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1080/10406638.2024.2412217
  • Dergi Adı: Polycyclic Aromatic Compounds
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Computer & Applied Sciences, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: ADME/T, azomethine, biological activity, cell culture, molecular docking, Schiff bases
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Hypopharyngeal cancer is rare subtype of head and neck cancers with relatively poor prognosis. Current therapeutic modalities lack the potential to provide patients with better clinical outcome and quality of life. This study was conducted on the synthesis of 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3) using biologically important 1,2,4-triazole. The condensation of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 4-formyl-2-methoxyphenyl-4-(4-formyl-2-methoxyphenyl)-4-oxobutanoate yielded the biologically active 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3). The compounds obtained were analyzed via FT-IR,1H-/13C-NMR spectrometers, elemental analysis, and HRMS spectroscopic techniques. Furthermore, we aimed at investigating the potential of compounds 3a-g against FaDu hypopharyngeal cancer cells. We demonstrated that compounds 3c, 3e, and 3 g had relatively lower IC50 values compared to the remaining tested compounds and more importantly their IC50 values were comparable to 5-FU, which suggests them as important therapeutic agent candidates. These newly synthesized compounds were assessed for their inhibitory activities toward two human carbonic anhydrase isoforms I and II (hCA I and II). Then, molecular docking calculations were made to compare the biological activities of studied molecules against cancer proteins. Compound 3c has a docking score of −7.15 against squamous cell carcinoma protein with ID: 2DO4 and −5.49 docking score against squamous cell carcinoma protein with ID:5PJZ. ADME/T analysis was performed to examine the drug properties of studied molecules.