Tacrine-Coumarin Derivatives As Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Mar 6

PMID 33672694

Citations 5

Authors

Eva Konkolova

Monika Hudacova

Slavka Hamulakova

Rastislav Jendzelovsky

Jana Vargova

Juraj Sevc

Peter Fedorocko

Maria Kozurkova

Affiliations

Soon will be listed here.

Abstract

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives -) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (TOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (, = tacrine-(CH)-coumarin). The most active of the tested compounds, derivatives and , both display longer chains.

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