engleski

Design, synthesis, biological evaluation and QSAR analysis of novel N-substituted benzimidazole derived carboxamides

As a result of our previous research focused on benzimidazole derivatives with potent antioxidative and antiproliferative activity, herein we present design, synthesis, QSAR analysis and biological activity of novel N-substituted benzimidazole derived carboxamides. The targeted carboxamides were designed in order to study the influence of the number of methoxy groups, the type of the substituent placed at the N atom of benzimidazole core as well as the type of the substituent placed at the benzimidazole core on biological activity. The most promising derivatives with pronounced antioxidative activity were unsubstituted derivative 28 (IC50 ≈ 3.78 mM, 538.81 mmolFe2+/mmolC) and dimetoxy substituted compound 34 (IC50 ≈ 5.68 mM, 618.10 mmolFe2+/mmolC) bearing methyl group at the N atom of benzimidazole core. On the other hand, trimethoxy substituted compound 43 and unsubstituted compound 40 both bearing isobutyl side chain at N atom at benzimidazole core showed strong activity in nanomolar concentrations against HCT116 (IC50 ≈ 0.6 µM, both) and H 460 cells (IC50 ≈ 2.5 µM and 0.4 µM, respectively), while being less cytotoxic toward non-tumour cell line HEK 293. In addition, antioxidative activity in cell generally confirmed relatively modest antioxidant capacity obtained in DPPH/FRAP assays of derivatives 34 and 40. Additionally, the 3D– QSAR models were generated to explore molecular properties that have the highest influence on antioxidative activity of studied compounds.

antioxidant activity ; antiproliferative activity ; benzimidazoles ; carboxamides ; QSAR ; ROS

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