Synthesis, antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines (CROSBI ID 248942)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Sović, Irena ; Jambon, Samy ; Kraljević Pavelić, Sandra ; Markova-Car, Elitza ; Ilić, Nataša ; Depauw, Sabine ; David-Cordonnier, Marie-Hélène ; Karminski-Zamola, Grace
engleski
Synthesis, antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines
In this paper novel isoindolines substituted with cyano and amidino benzimidazoles and benzothiazoles were synthetized as new potential anti-cancer drugs. The new structures were evaluated for antiproliferative activity, cell cycle changes, cell death, as well as DNA binding and topoisomerase inhibition properties on selected compounds. Results showed that all tested compounds exerted antitumor activity, especially amidinobenzothiazole and amidinobenzimidazole substituted isoindolin-1- ones and benzimidazole substituted 1- iminoisoindoline that showed antiproliferative effect in the submicromolar range. Moreover, the DNA-binding properties of selected compounds were evaluated by biophysical and biochemical approaches including thermal denaturation studies, circular dichroism spectra analyses and topoisomerase I/II inhibition assays and results identified some of them as strong DNA ligands, harboring or not additional topoisomerase II inhibition and able to locate in the nucleus as determined by fluorescence microscopy. In conclusion, we evidenced novel cyano- and amidino- substituted isoindolines coupled with benzimidazoles and benzothiazoles as topoisomerase inhibitors and/or DNA binding compounds with potent antitumor activities.
isoindolines ; benzothiazole ; benzimidazole ; antiproliferative activity ; DNA binding ; topoisomerase I/II inhibition
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Podaci o izdanju
26 (8)
2018.
1950-1960
objavljeno
0968-0896
1464-3391
10.1016/j.bmc.2018.02.045