Synthesis and anti-proliferative activity of some new quinoline based 4,5-dihydropyrazoles and their thiazole hybrids as EGFR inhibitors

Bioorg Chem. 2019 Mar:83:186-197. doi: 10.1016/j.bioorg.2018.10.038. Epub 2018 Oct 20.

Abstract

Quinoline derivatives 2, 3, quinolinyl based pyrazolines 4a,b, 5 and quinolinyl pyrazolinyl thiazole hybrids 6a-d, 7a-c and 8a-d were synthesized and screened for their anti-proliferative activity against MCF-7, HeLa and DLD1 cancer cell lines as well as normal fibroblast WI-38. Most of the tested compounds showed promising anticancer activity in addition to their safety towards the normal cell line. Eight compounds eliciting superior cytotoxicity against DLD1 and safe to the normal cell line 2, 3, 5, 6a, 6b, 7b, 7c and 8a were evaluated for their efficacy as EGFR inhibitors. They revealed inhibitory activity at nanomolar level especially compounds 6b, 2 and 7c with IC50 (31.80, 37.07 and 42.52 nM) in comparison to Gefitinib (IC50 = 29.16 nM).

Keywords: Anticancer; EGFR; Pyrazoline; Quinoline; Thiazole.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Humans
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Quinolines
  • Thiazoles
  • quinoline
  • EGFR protein, human
  • ErbB Receptors