Jump to main content
Jump to site search
SCHEDULED MAINTENANCE Close the message box

Maintenance work is planned for Monday 16 August 2021 from 07:00 to 23:59 (BST).

Website performance may be temporarily affected and you may not be able to access some PDFs or images. If this does happen, refreshing your web browser should resolve the issue. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 12, 2013

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

Author affiliations

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


Submitted
10 Jul 2013
Accepted
18 Sep 2013
First published
18 Sep 2013

Med. Chem. Commun., 2013,4, 1537-1550
Article type
Concise Article

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.


Search articles by author

Spotlight

Advertisements