Bisbenzimidazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Pharmacophore Analysis
| Autor: | Kayhan Bolelli, Serdar Burmaoglu, Serpil Gonca, Aylin Döğen, Ronak Haj Ersan, Oztekin Algul |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
biology 010405 organic chemistry Chemistry biology.organism_classification Antimicrobial 01 natural sciences Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Bisbenzimidazole Minimum inhibitory concentration Ampicillin Drug Discovery medicine Potency Pharmacophore Antibacterial activity Bacteria medicine.drug |
| Zdroj: | Pharmaceutical Chemistry Journal. 55:149-158 |
| ISSN: | 1573-9031 0091-150X |
| DOI: | 10.1007/s11094-021-02389-x |
| Popis: | In an attempt to design and synthesize a potent class of antimicrobials, 1,2-phenylenediamine derivatives were reacted with various aliphatic and heteroaliphatic dicarboxylic acids to generate a small library of 26 head-to-head bisbenzimidazole compounds (16 – 42) using the polyphosphoric acid method. These compounds were screened for their antibacterial activity and their antifungal activity. Compound 25 showed maximum potency against both Gram-positive and Gram-negative bacterial strains with minimum inhibitory concentration (MIC) values in the range of 7.81 – 31.25 μg/mL. In particular, it showed the maximum MIC values of 7.81 μg/mL against Gram-negative bacteria, which was four-fold more active than the standard drug ampicillin (MIC = 32.25 μg/mL). Compound 19 was found to be the most active against S. aureus with a MIC value of < 3.90 μg/mL, whereas the remaining compounds showed only low-to-moderate activity. Furthermore, all compounds exhibited low activity against all fungal strains in comparison to the standard drug fluconazole. I addition, pharmacophore hypotheses were generated to analyze structure–activity relationships between the molecular structures and antimicrobial activities on E. coli. This pharmacophore model can be useful in order to design new antimicrobial drugs. It can be suggested that the substitution of a phenyl ring at the 5/6 and 5′/6′ positions in symmetric bisbenzimidazole derivatives produces compounds with promising antimicrobial activity. |
| Databáze: | OpenAIRE |
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