Novel 1,2,4-triazole derivatives as potential anticancer agents: Design, synthesis, molecular docking and mechanistic studies

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A series of novel compounds carrying 1,2,4-triazole scaffold was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines using MTT assay. Compounds 8a, 8b, 8c, 8d, 10b, 10e, and 10 g showed remarkable antiproliferative activity against the tested cell lines. Compounds 8a, 8b, 8c, 8d, 10b, 10e, and 10 g with the least IC50 values in MTT assay were tested against three known anticancer targets including EGFR, BRAF and Tubulin. The results revealed that compounds 8c and 8d showed almost same BRAF inhibitory activity and were discovered to be potent inhibitors of cancer cell proliferation and were also observed to be strong Tubulin inhibitors. Moreover, 8c also showed the best EGFR inhibition with IC50 = 3.6 μM. 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)314-325
Number of pages12
JournalBioorganic Chemistry
Volume76
DOIs
Publication statusPublished - 1 Feb 2018
Externally publishedYes

Fingerprint

Antineoplastic Agents
Inhibitory Concentration 50
Assays
Tubulin Modulators
Cells
Derivatives
Cell Line
Molecular modeling
Cell proliferation
Tubulin
Scaffolds
Neoplasms
Cell Proliferation
Enzymes
1,2,4-triazole

Keywords

  • 1,2,4-Triazole
  • Antiproliferative
  • BRAF
  • EGFR
  • Tubulin and molecular docking

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Novel 1,2,4-triazole derivatives as potential anticancer agents : Design, synthesis, molecular docking and mechanistic studies. / El-Sherief, Hany A.M.; Youssif, Bahaa G.M.; Syed Nasir Abbas, Bukhari; Abdel-Aziz, Mohamed; Abdel-Rahman, Hamdy M.

In: Bioorganic Chemistry, Vol. 76, 01.02.2018, p. 314-325.

Research output: Contribution to journalArticle

El-Sherief, Hany A.M. ; Youssif, Bahaa G.M. ; Syed Nasir Abbas, Bukhari ; Abdel-Aziz, Mohamed ; Abdel-Rahman, Hamdy M. / Novel 1,2,4-triazole derivatives as potential anticancer agents : Design, synthesis, molecular docking and mechanistic studies. In: Bioorganic Chemistry. 2018 ; Vol. 76. pp. 314-325.
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