Schiff's base derivatives bearing nitroimidazole and quinoline nuclei: new class of anticancer agents and potential EGFR tyrosine kinase inhibitors

Jigar A Makawana; Chetan B Sangani; Lin Lin; Hai-Liang Zhu

doi:10.1016/j.bmcl.2014.02.041

Schiff's base derivatives bearing nitroimidazole and quinoline nuclei: new class of anticancer agents and potential EGFR tyrosine kinase inhibitors

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1734-6. doi: 10.1016/j.bmcl.2014.02.041. Epub 2014 Feb 28.

Authors

Jigar A Makawana¹, Chetan B Sangani¹, Lin Lin¹, Hai-Liang Zhu²

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
² State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.

PMID: 24630412
DOI: 10.1016/j.bmcl.2014.02.041

Abstract

New Schiff's base derivatives 5a-j have been synthesized by reaction between 2-phenoxyquinoline-3-carbaldehydes 3a-j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in presence of nickel(II) nitrate as a catalyst in ethanol under reflux in good yield (78-92%). All compounds were tested for anticancer and inhibition of EGFR. Of the compounds studied, majority of the compounds showed effective antiproliferation and inhibition of EGFR and HER-2 activities. Compound 5h showed most effective inhibition (IC50=0.12±0.05 μM) by binding in to the active pocket of EGFR receptor with minimum binding energy (ΔGb=-58.3691 kcal/mol). The binding was stabilized by two hydrogen bonds, two π-cation and one π-sigma interactions. Compound 5d showed most effective inhibition (IC50=0.37±0.04 μM).

Keywords: Anticancer activity; EGFR inhibition; Nitroimidazole; Quinoline; Schiff’s base.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / metabolism
Hep G2 Cells
Humans
Molecular Docking Simulation
Molecular Structure
Nitroimidazoles / chemistry*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Quinolines / chemistry*
Schiff Bases / chemical synthesis
Schiff Bases / chemistry
Schiff Bases / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Nitroimidazoles
Protein Kinase Inhibitors
Quinolines
Schiff Bases
ErbB Receptors