Synthesis and SAR Study of Novel Amidino 2-substituted Benzimidazoles as Potential Antibacterial Agents

Croatica Chemica Acta

Verbanac, Donatella¹  Čipčić Paljetak, Hana¹  Matijašić, Mario¹  Perić, Mihaela¹  Starčević, Kristina²  Hranjec, Marijana³  Karminski-Zamola, Grace³  Perin, Nataša³  Stepanić, Višnja⁴ 

[1] Department for Intercellular Communication, Center for Translational and Clinical Research, University of Zagreb School of Medicine, Šalata 2, HR-10000 Zagreb, Croatia;Department of Animal Husbandry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000 Zagreb, Croatia;Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P. O. Box 177, HR-10000 Zagreb, Croatia;Division of Molecular Medicine, Laboratory for Epigenomics, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia

关键词: amidines;    benzimidazoles;    antibacterial activity;    Moraxella catarrhalis;    lipophilicity;   

DOI  :  10.5562/cca3147

学科分类：化学（综合）

来源: Croatica Chemica Acta

【 摘 要 】

A series of novel 2-substituted benzimidazole derivatives were synthesized and their antibacterial activity was assessed against selected Gram-positive and Gram-negative bacteria. The specific moiety at the 2-position of the benzimidazole was extensively modified with several fused heterocyclic functional groups containing nitrogen and sulfur heteroatoms. In addition, the influence of different amidino groups at the position 5 of benzimidazole scaffold was evaluated. The values of clogP (a partition coefficient) and clogD7.5 (calculated distribution coefficient, pH 7.5) were determined and the lipophilic character of compounds has been found to be important parameter for the observed activity of the tested benzimidazole derivatives against Moraxella catarrhalis. The indolo 2-substituted benzimidazole 13a demonstrated solid activity against Staphylococcus aureus (MICs 16 µg/mL) and Moraxella catarralis (MICs 2 µg/mL) and represents promising lead molecule for further optimization.

【 授权许可】

CC BY