Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors

Md Jawaid Akhtar, Ahsan Ahmed Khan, Zulphikar Ali, Rikeshwer Prasad Dewangan, Md Rafi, Md Quamrul Hassan, Md Sayeed Akhtar, Anees Ahmad Siddiqui, Sangh Partap, Santosh Pasha, M. Shahar Yar

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC50 = 2.2 µM) and EGFR binding (IC50 = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = −34.581 Kcal/mol.

Original languageEnglish
Pages (from-to)158-169
Number of pages12
JournalBioorganic Chemistry
Volume78
DOIs
StatePublished - 1 Aug 2018
Externally publishedYes

Keywords

  • Anticancer
  • Apoptosis
  • Benzimidazole linked pyrazole
  • Cardiomyopathy studies
  • Docking studies

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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