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Bisbenzimidazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Pharmacophore Analysis
Pharmaceutical Chemistry Journal ( IF 0.9 ) Pub Date : 2021-05-06 , DOI: 10.1007/s11094-021-02389-x
Ronak Haj Ersan , Kayhan Bolelli , Serpil Gonca , Aylin Dogen , Serdar Burmaoglu , Oztekin Algul

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.



中文翻译:

作为潜在抗微生物剂的联苯并咪唑衍生物:设计,合成,生物学评估和药效基团分析

在试图设计和合成的强效类抗菌剂,1,2-苯二胺衍生物用各种脂肪族和杂脂肪族二羧酸的反应,生成的26头至头小型图书馆二苯并咪唑化合物(16 - 42),使用多酸法。筛选这些化合物的抗菌活性和抗真菌活性。化合物25对革兰氏阳性菌和革兰氏阴性菌均显示出最大的效力,其最小抑菌浓度(MIC)值在7.81 – 31.25μg/ mL的范围内。特别是,它对革兰氏阴性菌的最大MIC值为7.81μg/ mL,比标准药物氨苄西林(MIC = 32.25μg/ mL)高四倍。化合物19被发现对金黄色葡萄球菌最具活性,MIC值<3.90μg/ mL,而其余化合物仅表现出低至中度的活性。此外,与标准药物氟康唑相比,所有化合物对所有真菌菌株均显示低活性。此外,还产生了药效团假说,以分析分子结构与对大肠杆菌的抗菌活性之间的构效关系。该药效团模型可用于设计新的抗菌药物。可以认为,在对称的双苯并咪唑衍生物的5/6和5'/ 6'位置上的苯环取代会产生具有令人满意的抗菌活性的化合物。

更新日期:2021-05-06
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