Design, Synthesis and Biological Activity of Novel Methoxy- and Hydroxy-Substituted N-Benzimidazole-Derived Carboxamides

Beč, Anja; Zlatić, Katarina; Banjanac, Mihailo; Radovanović, Vedrana; Starčević, Kristina; Kralj, Marijeta; Hranjec, Marijana (2024) Design, Synthesis and Biological Activity of Novel Methoxy- and Hydroxy-Substituted N-Benzimidazole-Derived Carboxamides. Molecules, 29 (9). ISSN 1420-3049

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Abstract

This work presents the design, synthesis and biological activity of novel N-substituted benzimidazole carboxamides bearing either a variable number of methoxy and/or hydroxy groups. The targeted carboxamides were designed to investigate the influence of the number of methoxy and/or hydroxy groups, the type of substituent placed on the N atom of the benzimidazole core and the type of substituent placed on the benzimidazole core on biological activity. The most promising derivatives with pronounced antiproliferative activity proved to be N-methyl-substituted derivatives with hydroxyl and methoxy groups at the phenyl ring and cyano groups on the benzimidazole nuclei with selective activity against the MCF-7 cell line (IC50 = 3.1 μM). In addition, the cyano-substituted derivatives 10 and 11 showed strong antiproliferative activity against the tested cells (IC50 = 1.2–5.3 μM). Several tested compounds showed significantly improved antioxidative activity in all three methods compared to standard BHT. In addition, the antioxidative activity of 9, 10, 32 and 36 in the cells generally confirmed their antioxidant ability demonstrated in vitro. However, their antiproliferative activity was not related to their ability to inhibit oxidative stress nor to their ability to induce it. Compound 8 with two hydroxy and one methoxy group on the phenyl ring showed the strongest antibacterial activity against the Gram-positive strain E. faecalis (MIC = 8 μM).

Item Type:	Article
Uncontrolled Keywords:	antibacterial activity ; antioxidative activity ; antiproliferative activity ; benzimidazoles ; carboxamides ; ROS
Subjects:	NATURAL SCIENCES > Chemistry > Organic Chemistry BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Pharmacy > Medical Biochemistry
Divisions:	Division of Molecular Medicine Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa-AntioxPot Marijana Hranjec; Livio Racane; Lucija Ptiček; Marijeta Kralj; Karmen Brajša; Ines Vujasinović; Kristina Butković; Ivana Novak Jovanović IP-2018-01-4379 HRZZ
Depositing User:	Ana Zečević
Date Deposited:	19 Jul 2024 09:44
URI:	http://fulir.irb.hr/id/eprint/8951
DOI:	10.3390/molecules29092138

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