Investigation of the Properties of 1,2,4-Triazole-3-thione Schiff Base Derivatives by Urease Inhibition as Therapeutic or Agrochemical Candidate Molecules


Zehir Kirkbir G., Gultekin E., KOLCUOĞLU Y., BEKİRCAN O., ÇOLAK A.

CHEMISTRYSELECT, cilt.9, sa.26, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 9 Sayı: 26
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/slct.202304002
  • Dergi Adı: CHEMISTRYSELECT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: 1,2,4-triazole-3-thione, ADME, Docking, Inhibition, Urease
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

With the production of bacterial urease, bacteria can provide the best conditions for colonization and survival of the stomach in acidic environment. Due to this reproductive ability, H. pylori can cause various diseases such as cancer, urinary tract infections, and peptic ulcer in human metabolism. Consequently, the discovery of substances that can inhibit urease activity holds great promise for treating certain diseases. In this study, Schiff base derivatives of 1,2,4-triazole-3-thione were synthesized in good to excellent yields. The structures of the obtained compounds were elucidated using spectroscopic techniques, such as FT-IR, 1H-NMR and 13C-NMR. The urease inhibitory activities of the obtained products were evaluated against the reference inhibitor thiourea. Out of these compounds, compound 6 c exhibited the highest inhibitory effectiveness, with an IC50 value of 0.0109 mu M against refenrence inhibitor (IC50=11 mu M). Kinetic studies revealed that compound 6 c acts as a non-competitive inhibitor. According to the results of the docking studies, compound 6 c exhibited the highest binding affinity (with the lowest Delta G value as -8.4 kcal/mol) and efficiently interacted with the enzyme as a potent inhibitor among all the molecules examined in the study. In this research, a series of new 1,2,4-triazole Schiff base derivative compounds synthesized, characterized and their anti-urease activities tested against thiourea. Among these compounds, compound 6 c displayed the best inhibition effect with an IC50 value of 0.0109 mu M. Docking studies indicated that compound 6c had the highest binding affinity (with a Delta G value of -8.4 kcal/mol), effectively interacting with the enzyme and acting as the most potent inhibitor among all the molecules tested. image