Design and synthesis of new heterocyclic compounds containing 5-[(1H-1,2,4-triazol-1-yl)methyl]-3H-1,2,4-triazole-3-thione structure as potent hEGFR inhibitors

KOLCUOĞLU Y., BEKİRCAN O., Fazli H., Sahin E., TÜRE A., AKDEMİR A., ...More

Journal of Biomolecular Structure and Dynamics, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1080/07391102.2023.2167113
  • Journal Name: Journal of Biomolecular Structure and Dynamics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: 1, 1, 2, 2, 4-triazole-3-thiones, 4-triazoles, docking, hEGFR, molecular modeling, thiosemicarbazides
  • Bezmialem Vakıf University Affiliated: Yes


© 2023 Informa UK Limited, trading as Taylor & Francis Group.EGFR is one of the important mediators of the signaling cascade that determines key roles in various biological processes such as growth, differentiation, metabolism and apoptosis in the cell in response to external and internal stimuli. In recent years, it has been proven that although this enzyme activity is tightly regulated in normal cells, if the enzyme activity cannot be controlled, it can lead to malignancy. EGFR is also considered a prominent macromolecule in targeted cancer chemotherapy. For this purpose, a comprehensive modeling studies were conducted against EGFR protein and novel molecules containing 5-[(1H-1,2,4-triazol-1-yl)methyl]-3H-1,2,4-triazole-3-thione structure were suggested to be synthesized. Among the synthesized molecules, compounds 7c, 8c, 8f and 8g were determined to have significant IC50 values. Compound 8g was found to have the IC50 value closest to the very well-known EGFR inhibitor Gefitinib with its noncompetitive inhibition form. K i value of compound 8g was calculated as 0.00232 µM. Communicated by Ramaswamy H. Sarma.