Development of benzimidazole-based derivatives as antimicrobial agents and their synergistic effect with colistin against gram-negative bacteria

Dokla, Eman M.E.; Abutaleb, Nader S.; Milik, Sandra N.; Li, Daoyi; El-Baz, Karim; Shalaby, Menna-Allah W.; Al-Karaki, Rawan; Nasr, Maha; Klein, Christian D.; Abouzid, Khaled A. M.; Seleem, Mohamed N.

doi:10.1016/j.ejmech.2019.111850

Cited by 49 publications

(15 citation statements)

References 29 publications

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“…Among the compounds 78–80 , the compound 80 highly inhibited the B. subtilis and S. aureus bacterial growth compared to the reference drug chloramphenicol (zone of inhibition, mm: 23 and 14 vs. 32 and 30) ( İbişoğlu et al, 2020 ). Besides, co-treatment of compound 81 with colistin exhibited a promising synergistic effect against wild strains E. coli , K. pneumoniae , A. baumannii , and P. aeruginosa with MIC range = 8–16 μg/ml ( Dokla et al, 2020 ). Malasala et al ( Malasala et al, 2021 ) reported nine more potent antibacterial agents 82–90 with MIC range 4–64 μg/ml against several resistant organisms, including methicillin and vancomycin-resistant S. aureus .…”

Section: Biological Activitiesmentioning

confidence: 99%

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

et al. 2021

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Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

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Section: Biological Activitiesmentioning

confidence: 99%

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

et al. 2021

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“…1H-benzimidazol-2-yl)phenyl)methane sulfonamide, 9 which exhibited significant activity against Escherichia coli (JW55031) with a minimum inhibitory concentration (MIC) value of 2 μg mL −1 .…”

Section: Dokla Et Al Prepared N-(3-(1-(4-methylbenzyl)-mentioning

confidence: 99%

Synthesis and fungicidal activity of novel benzimidazole derivatives bearing pyrimidine‐thioether moiety against Botrytis cinerea

Sun

Zhang

Qian

et al. 2021

Pest Management Science

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BACKGROUND: Botrytis cinerea is a serious plant fungus and strongly affects the yield and quality of crops. The main control strategy is the employment of fungicides. To research for efficient fungicide with novel structure, a series of novel benzimidazole derivatives bearing pyrimidine and thioether moieties were designed and synthesized.RESULTS: Some target compounds such as 4h, 4i, 4k, 4l, 4m, 4s, 4t and 4u exhibited notable fungicidal activities, with half maximal effective concentration (EC 50 ) values in the range 0.13-0.24 ∼g mL −1 , which means that their activities were comparable or higher than that of carbendazim (EC 50 = 0.21 ∼g mL −1 ). Among them, N-(4-fluorophenyl)-2-((4-(1H-benzimidazol-2-yl)-6-(4-methoxyphenyl) pyrimidin-2-yl)thio)acetamide (4m) displayed the best activity (EC 50 = 0.13 ∼g mL −1 ). Molecular electrostatic potential analysis of 4m elucidated that the NH moiety of benzimidazole ring was located in the positive potential region and may generate hydrogen bond with target amino acid residue. Molecular docking analysis revealed that there was one hydrogen bond and one π-π interaction between 4m and target protein.CONCLUSIONS: This study demonstrated that the benzimidazole derivatives bearing pyrimidine and thioether moieties can be further optimized as a lead compound for the control of B. cinerea. The combination of molecular electrostatic potential and molecular docking analyses may provide a valuable reference for studying the interaction between the ligand and target protein.

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“…Zhang et al synthesized a series of quinolone-benzimidazoles hybrid molecules and demonstrated their membrane-disrupting features against Gram-positive and Gram-negative pathogens [ 26 ]. Recently, Dokla’s group developed benzimidazole-based antimicrobial molecules, and demonstrated that a p -methyl benzyl substituted molecule can unlock the bacterial membrane and allow colistin to penetrate inside the bacteria [ 27 ]. Here, we present the design and synthesis of N -methyl benzimidazole conjugated CA amphiphiles, and their antibacterial activities against Gram-positive and Gram-negative bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

N-methyl Benzimidazole Tethered Cholic Acid Amphiphiles Can Eradicate S. aureus-Mediated Biofilms and Wound Infections

Kakkar¹,

Chaudhary²,

Mehta³

et al. 2022

Molecules

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Infections associated with Gram-positive bacteria like S. aureus pose a major threat as these bacteria can develop resistance and thereby limit the applications of antibiotics. Therefore, there is a need for new antibacterials to mitigate these infections. Bacterial membranes present an attractive therapeutic target as these membranes are anionic in nature and have a low chance of developing modifications in their physicochemical features. Antimicrobial peptides (AMPs) can disrupt the microbial membranes via electrostatic interactions, but the poor stability of AMPs halts their clinical translation. Here, we present the synthesis of eight N-methyl benzimidazole substituted cholic acid amphiphiles as antibacterial agents. We screened these novel heterocyclic cholic acid amphiphiles against different pathogens. Among the series, CABI-6 outperformed the other amphiphiles in terms of bactericidal activity against S. aureus. The membrane disruptive property of CABI-6 using a fluorescence-based assay has also been investigated, and it was inferred that CABI-6 can enhance the production of reactive oxygen species. We further demonstrated that CABI-6 can clear the pre-formed biofilms and can mitigate wound infection in murine models.

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Development of benzimidazole-based derivatives as antimicrobial agents and their synergistic effect with colistin against gram-negative bacteria

Cited by 49 publications

References 29 publications

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

Synthesis and fungicidal activity of novel benzimidazole derivatives bearing pyrimidine‐thioether moiety against Botrytis cinerea

N-methyl Benzimidazole Tethered Cholic Acid Amphiphiles Can Eradicate S. aureus-Mediated Biofilms and Wound Infections

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