Naslov
Synthesis, antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines
(Synthesis, antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines)

Autori
Sović, Irena ; Jambon, Samy ; Kraljević Pavelić, Sandra ; Markova-Car, Elitza ; Ilić, Nataša ; Depauw, Sabine ; David-Cordonnier, Marie-Hélène ; Karminski-Zamola, Grace

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 26 (2018), 8; 1950-1960

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
isoindolines ; benzothiazole ; benzimidazole ; antiproliferative activity ; DNA binding ; topoisomerase I/II inhibition

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA