Synthesis and evaluation of selected benzimidazole derivatives as potential antimicrobial agents. An investigation into the synthesis of substituted benzimidazoles and their evaluation in vitro for antimicrobial activity.

摘要

Microbe resistence is a serious issue, especially as they have become resistant toudmost well known drugs. Therefore this is considered as a global problem and is nowuddealt with at a poitical level. Since no new classes of antimicrobial agents haveudbeen discovered in the past three deacdes, the development of new drugs isudextremely urgent. Therefore the aim of this project was to synthesise derivatives ofudbenzimidazole, and then assesses their antimicrobial activities in vitro by using discud(well) diffusion and MICs tests.udA total of 69 benzimidazole derivatives, with substituents at positions 1, 2, and 5,udwere synthesised, characterised and tested against selected bacteria and fungi. Inudaddition, six bezimidazole silver complexes were prepared and evaluated for theirudantimicrobial behavior.udThe SAR showed that the antimicrobial activity of the compounds depended on theudsubstituents attached to the bicyclic heterocycle. Some promising results wereudobtained. In particular, 5 compounds displayed antibacterial activity against twoudMRSA strains with MIC values corresponding to ciprofloxacin, which can beudconsidered significant. The compounds have some common features; four possessud5-chloro or 5-bromo substituents; two are derivatives of (S)-2-udethanaminebenzimidazole and the others are derivative of one 2-(chloromethyl)-1Hbenzo[d]imidazole, (1H-benzo[d]imidazol-2-yl)methanethiol and 2-(methoxymethyl)-1-methyl-1H-benzo[d]imidazole.udThe results from the antifungal screening were very interesting as there were 26udcompounds, including two silver complexes, which were potent fungicides againstudthe selected fungal species. They showed equivalent or greater potentency in theirudMIC values than amphotericin B. In particular, the 5-fluoro, 5-chloro and 5-bromoudbenzimidazole showed broad spectrum activity.