engleski

Synthesis, antibacterial activity and SAR study of novel amidino 2-substituted benzimidazole derivatives

Bacterial organisms causing infectious diseases represent an increasing public health problem regardless of the current availability of numerous antimicrobial agents. Staphylococcus aureus represents a major Gram-positive human pathogen while Moraxella catarrhalis is establishing its role as an emerging respiratory Gram-negative pathogenic microorganism.[1] A series of novel 2-substituted benzimidazole derivatives were synthesized and their antibacterial activity was assessed against Gram-positive and Gram-negative bacteria.[2] The specific moiety at the 2-position of the benzimidazole was extensively modified with several fused heterocyclic functional groups containing nitrogen and sulphur heteroatoms.[3] 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 M. catarrhalis. The indolo 2-substituted benzimidazole 13a demonstrated solid activity against S. aureus (MICs 16 µg/mL) and M. catarralis (MICs 2 µg/mL). Furthermore, the SAR results obtained in this study will be applied for the further optimization of this heteroaromatic core and for the design of novel derivatives in order to improve initially observed antibacterial activity.

amidines ; benzimidazoles ; antibacterial activity, Moraxella catarrhalis ; lipophilicity

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