Issue 12, 2013

Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chains

Abstract

This manuscript describes the synthesis and biological activity of 2-substituted benzimidazo[1,2-a]quinolines substituted with different amino side chains on the quinoline nucleus prepared by microwave assisted amination. The majority of compounds were newly synthesized and active at submicromolar IC50 concentrations, while the alkylamino substituents, either acyclic or cyclic, increased antitumor activities in comparison with previously published nitro and amino substituted benzimidazo[1,2-a]quinolines. The compound with the longest tertiary amino side chain (16) was the least active. A series of additional experiments, including DNA binding propensities, topoisomerases I and II inhibition, inhibition of recombinant green fluorescent protein in a cell-free translation system, cell cycle perturbances and cellular localization, was performed to shed more light on the mechanisms of action of the most active compounds. The DNA intercalation activity correlates with anti-proliferative effect. Several DNA intercalators (11, 20 and 21) also evidence some sequence selective DNA binding. However, only N,N-dimethylaminopropyl analogue 11 was unequivocally demonstrated to be a strong DNA-binder and intercalative agent, which efficiently targets DNA in the cells, while the activity of compound 10, with a bulky i-butylamino side chain, points to its potential antimitotic activity.

Graphical abstract: Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chains

Article information

Article type
Concise Article
Submitted
10 Jul 2013
Accepted
18 Sep 2013
First published
18 Sep 2013

Med. Chem. Commun., 2013,4, 1537-1550

Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chains

N. Perin, I. Martin-Kleiner, R. Nhili, W. Laine, M. David-Cordonnier, O. Vugrek, G. Karminski-Zamola, M. Kralj and M. Hranjec, Med. Chem. Commun., 2013, 4, 1537 DOI: 10.1039/C3MD00193H

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