Design, regioselective synthesis and cytotoxic evaluation of 2-aminoimidazole-quinoline hybrids against cancer and primary endothelial cells

Kuldeep Singh; Vikas Verma; Kavita Yadav; Vedagopuram Sreekanth; Devinder Kumar; Avinash Bajaj; Vinod Kumar

doi:10.1016/j.ejmech.2014.09.055

Design, regioselective synthesis and cytotoxic evaluation of 2-aminoimidazole-quinoline hybrids against cancer and primary endothelial cells

Eur J Med Chem. 2014 Nov 24:87:150-8. doi: 10.1016/j.ejmech.2014.09.055. Epub 2014 Sep 17.

Authors

Kuldeep Singh¹, Vikas Verma², Kavita Yadav³, Vedagopuram Sreekanth³, Devinder Kumar⁴, Avinash Bajaj³, Vinod Kumar⁵

Affiliations

¹ Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India; Department of Chemistry, M.M. University, Mullana, Ambala 133207, Haryana, India.
² Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India.
³ Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, Gurgaon 122016, Haryana, India.
⁴ Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India. Electronic address: dk_ic@yahoo.com.
⁵ Department of Chemistry, M.M. University, Mullana, Ambala 133207, Haryana, India.

PMID: 25247771
DOI: 10.1016/j.ejmech.2014.09.055

Abstract

In search of new selective anti-cancer agents, a series of sixteen novel 2-aminoimidazole-quinoline hybrid compounds (5a-5p) have been designed and synthesized regioselectively. We have characterized the compounds extensively using IR, 1D and 2D NMR Spectroscopy and mass spectrometry. The cytotoxicity studies against different cancer cell lines showed that the compound 5a (Imd-Ph) emerged as a potent cytotoxic scaffold. Imd-Ph (5a) exhibited a selective anticancer activity against human colon cancer cell line (HCT-116, DLD-1) and was found relatively non-toxic to breast cancer cells (MDA-MB-231) as well as to normal primary endothelial cells (HUVEC). Structure-activity relationship of imidazole-quinoline hybrid scaffolds revealed differential and selective toxicities exerted by the different derivatives against cancer and normal cells. Structural modification of the scaffold with library of a wide variety of substituents may lead to the development of novel selective anti-cancer agents in the future.

Keywords: 2-Aminoimidazole; Cytotoxicity; Quinoline; Regioselectivity; Selective anticancer agents.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Breast Neoplasms / drug therapy*
Breast Neoplasms / pathology
Cell Proliferation / drug effects
Cells, Cultured
Colonic Neoplasms / drug therapy*
Colonic Neoplasms / pathology
Drug Design*
Drug Screening Assays, Antitumor
Female
Human Umbilical Vein Endothelial Cells / drug effects*
Humans
Imidazoles / chemistry*
Molecular Structure
Quinolines / chemistry*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Imidazoles
Quinolines
2-aminoimidazole
quinoline