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Synthesis and biological activity of novel benzimidazolyl and benzothiazolyl substituted isoindolines

At the present time, a great challenge for medicinal chemistry is finding new and more selective anticancer agents and therefore there is tremendous growth in the number and types of new compounds which exhibit antitumor activity. Derivatives of isoindoline have been found interesting due to their presence in number of natural and synthetic bioactive compounds. In this report we present, as a part of our continuous research to develop novel nitrogen containing heterocycles as potential anticancer agents, synthesis and biological activity of novel benzimidazolyl and benzothiazolyl substituted isoindolines. Target compounds were prepared by condensation of o-phthalaldehyde and heterocyclic amines in acidic conditions. The antiproliferative activity was assessed on a panel of tumor cell lines and normal human fibroblasts. The majority of tested compounds exerted concentration dependent antiproliferative effects and for several compounds selective effect at micromolar concentrations was observed. For selected compounds, further mechanistic studies involving analysis of cell cycle and cell death mechanisms were pursued on. Interaction with ct-DNA was also studied by use of thermal denaturation experiment, circular dichroism spectra method, topoisomerase I-induced DNA relaxation and DNase I footprinting experiment.

isoindoline; antitumor activity; DNA binding

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