Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors

Hany A.M. El-Sherief, Bahaa G.M. Youssif, Bukhari Syed Nasir Abbas, Ahmed H. Abdelazeem, Mohamed Abdel-Aziz, Hamdy M. Abdel-Rahman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A series of novel compounds carrying 1,2,4-triazole scaffold were prepared and evaluated for their antiproliferative activities against NCI 60 cell line. Compounds 10 (a, c), 11 (a-d), and 14 (a-e) were selected for evaluation at single concentration of 10 μM towards panel of sixty cancer cell lines. Some of nitric oxide (NO) donating triazole/oxime hybrids 11a-d showed antiproliferative activity better than their corresponding ketones. On the other hand, the thiazolo [3,2-b][1,2,4]-triazoles 14a-e showed remarkable antiproliferative activities against the same cell lines. Compound 14d was selected for five dose testing against the full panel of 60 human tumor cell lines. Compound 14d showed high selectivity against renal subpanel with selectivity ratio of 6.99 at GI50 level. Compounds 11a-d, 10a-d and 14a-e were tested against four cell lines using MTT assay then compounds of the least IC50 were evaluated against three known anticancer targets including EGFR, BRAF and Tubulin. The results revealed that compound 14d showed promising EGFR inhibitory activity of cancer cell proliferation and were also observed to be moderate BRAF and tubulin inhibitors. Moreover, cell cycle analysis and apoptosis assay were finished for compounds 14d and 14f. Finally molecular modeling studies were performed to explore the binding mode of the most active compounds to the target enzymes.

Original languageEnglish
Pages (from-to)774-789
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Volume156
DOIs
Publication statusPublished - 5 Aug 2018
Externally publishedYes

Fingerprint

Molecular modeling
Cells
Derivatives
Cell Line
Tubulin Modulators
Triazoles
Oximes
Assays
Tubulin
Tumor Cell Line
Ketones
Inhibitory Concentration 50
Neoplasms
Cell Cycle
Nitric Oxide
Cell Proliferation
Cell proliferation
Apoptosis
Kidney
Scaffolds

Keywords

  • 1,2,4-Triazoles
  • Antiproliferative
  • Apoptosis and EGFR inhibitors
  • Cell cycle
  • Thiazolo[3,2-b][1,2,4]-triazoles

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors. / El-Sherief, Hany A.M.; Youssif, Bahaa G.M.; Syed Nasir Abbas, Bukhari; Abdelazeem, Ahmed H.; Abdel-Aziz, Mohamed; Abdel-Rahman, Hamdy M.

In: European Journal of Medicinal Chemistry, Vol. 156, 05.08.2018, p. 774-789.

Research output: Contribution to journalArticle

El-Sherief, Hany A.M. ; Youssif, Bahaa G.M. ; Syed Nasir Abbas, Bukhari ; Abdelazeem, Ahmed H. ; Abdel-Aziz, Mohamed ; Abdel-Rahman, Hamdy M. / Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 156. pp. 774-789.
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