Fluorinated 3,6,9-trisubstituted acridine derivatives as DNA interacting agents and topoisomerase inhibitors with A549 antiproliferative activity
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31679839
DOI
10.1016/j.bioorg.2019.103393
PII: S0045-2068(19)31491-9
Knihovny.cz E-resources
- Keywords
- 3,6,9-Trisubstituted acridine derivatives, Cytotoxicity, Fluorine, Lung carcinoma cells, Spectroscopic techniques, calf thymus DNA, topoisomerases I/II,
- MeSH
- Acridines chemical synthesis chemistry pharmacology MeSH
- A549 Cells MeSH
- DNA Topoisomerases, Type I metabolism MeSH
- DNA Topoisomerases, Type II metabolism MeSH
- DNA drug effects MeSH
- Halogenation MeSH
- Topoisomerase I Inhibitors chemical synthesis chemistry pharmacology MeSH
- Topoisomerase II Inhibitors chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Cattle MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Cattle MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acridines MeSH
- calf thymus DNA MeSH Browser
- DNA Topoisomerases, Type I MeSH
- DNA Topoisomerases, Type II MeSH
- DNA MeSH
- Topoisomerase I Inhibitors MeSH
- Topoisomerase II Inhibitors MeSH
- Antineoplastic Agents MeSH
A series of new 3,6,9-trisubstituted acridine derivatives with fluorine substituents on phenyl ring were synthesized and their interaction with calf thymus DNA was investigated. Analysis using UV-Vis absorbance spectra provided valuable information about the formation of the acridine-DNA complex. In addition, compounds 8b and 8d were found to display an increased binding affinity (K = 2.32 and 2.28 × 106 M-1, respectively). Topo I/II inhibition mode assays were also performed, and the results verify that the novel compounds display topoisomerase I and II inhibitory activity; compounds 8a, 8b and 8c completely inhibited topoisomerase I activity at a concentration of 60 × 10-6 M, but only compound 8d showed partial ability to inhibit topoisomerase II at concentrations of 30 and 50 × 10-6 M. The ability of the derivatives to impair cell proliferation was tested through an analysis of cell cycle distribution, quantification of cell number, viability studies, metabolic activity measurement and clonogenic assay. The content and localization of the derivatives in cells were analyzed using flow cytometry and fluorescence microscopy. The compounds 8b and 8d altered the physiochemical properties and improved antiproliferative activity in A549 human lung carcinoma cells (compound 8d displayed the highest level of activity, 4.25 × 10-6 M, after 48 h).
References provided by Crossref.org
