SAR investigation and optimization of benzimidazole-based derivatives as antimicrobial agents against Gram-negative bacteria

Dokla, Eman M.E.; Abutaleb, Nader S.; Milik, Sandra N.; Kandil, Ezzat A E A; Qassem, Omar Magdy; Elgammal, Yehia; Nasr, Maha; McPhillie, Martin J.; Abouzid, Khaled A. M.; Seleem, Mohamed N.; Imming, Peter; Adel, Mai

doi:10.1016/j.ejmech.2022.115040

Cited by 10 publications

(7 citation statements)

References 79 publications

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“…However, the antiviral activities of these old drugs are not very satisfactory. Benzimidazole derivatives display a variety of biological activities in many diseases through various mechanisms, such as antiviral [ 28 , 29 ], antimicrobial [ 30 , 31 ], antiproliferative [ 32 , 33 ], and anticancer activities [ 34 , 35 ]. Benzimidazole derivatives are special lead compounds for antiviral drugs, attracting interest from many chemists [ 18 , 36 , 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

Chen

Wang

et al. 2023

Molecules

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The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d−Z, 7h−Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10−7 M) in SPR study. The compound 7h−Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure–activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

Chen

Wang

et al. 2023

Molecules

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“…Numerous studies have demonstrated the antimicrobial activity of benzimidazole derivatives against a variety of microorganism strains. 13 The most straightforward pathway for synthesizing 1H-benzimidazole involves condensing carboxylic acid (or its derivatives such as orthoesters, nitriles, and chlorides) with o-phenylenediamine in the presence of an aldehyde or acid, utilizing sodium (Na 2 S 2 O 5 ). 14 The biological activity of benzimidazole stems from its distinctive physicochemical properties, including π→π stacking interactions, hydrophobic interactions, coordination as a ligand with metals, H-bond acceptor/donor capability, and its ability to bind with nucleic acids, enzymes, and biomolecules.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking Investigation and Pharmacokinetic Properties Prediction of Some Benzimidazole Analogues as Dihydropteroate Synthase (DHPS) Inhibitors

Salubi

2023

Preprint

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Recent research has established the classification of benzimidazole as a privileged structure owing to its strong binding affinity to protein receptors and diverse enzymes. Extensive investigations have consistently shown the antimicrobial potential of benzimidazole derivatives against a wide range of microbial strains. In order to gain a deeper understanding of the relationship between structural modifications and the antibacterial effectiveness of sulfonamide compounds, we have developed targeted derivatives with subtle alterations in the aromatic ring of sulfonamides and the substituent groups. Furthermore, we present the results of molecular docking analyses, ADMET properties, and drug-likeness assessment to evaluate the potential of these compounds to interact with dihydropteroate synthase, a key enzyme involved in bacterial growth. The compounds exhibited a favourable binding affinity, ranging from 7.1 to 7.9 kcal/mol, which surpasses that of the standard drugs sulfamethazine and sulfamethoxazole, with binding affinities of 5.9 and 6.1 kcal/mol, respectively. Furthermore, these compounds demonstrated good oral bioavailability and exhibited favourable drug-like properties.

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“…Since then, benzimidazoles have been considered a central heterocyclic core due to their broad extent of pharmaceutical and therapeutic applications [35,36] . Hence, much research has been reported on the utility of benzimidazole‐bearing compounds as antifungal, anticancer, antibacterial, antidiabetic, antiproliferative, anthelmintic, antiviral, and antioxidant agents [37–44] . The pharmacological efficiency of benzimidazole derivatives to serve as inhibitor agents of numerous enzymes sheds new light on our findings for treating various incurable diseases, especially different classes of cancers [45,46] .…”

Section: Introductionmentioning

confidence: 99%

“…[35,36] Hence, much research has been reported on the utility of benzimidazole-bearing com-pounds as antifungal, anticancer, antibacterial, antidiabetic, antiproliferative, anthelmintic, antiviral, and antioxidant agents. [37][38][39][40][41][42][43][44] The pharmacological efficiency of benzimidazole derivatives to serve as inhibitor agents of numerous enzymes sheds new light on our findings for treating various incurable diseases, especially different classes of cancers. [45,46] Some renowned benzimidazole-based drugs, including carbendazim, tilomisole, omeprazole, bendamustine, albendazole, and mebendazole, have profoundly influenced the development of modern protocols to combat various diseases (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Anticancer Applications of Benzimidazole Derivatives

Mavvaji,

Akkoc

2023

ChemistrySelect

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Cancer, one of the most deadly diseases worldwide, is still a crucial challenge to human well‐being. Hence, the design and development of modern protocols to cure diverse kinds of cancer seem highly necessary. On the other hand, benzimidazole, as an essential pharmacophore, exhibits various biological and therapeutic potency. This compound is well‐known for its pharmaceutical features, including antifungal, antiviral, antibacterial, and anticancer activities. Therefore, benzimidazole derivatives have played an essential role due to their outstanding anticancer capability, apoptotic effect, and inhibitory potential. In recent decades, numerous anticancer drug types of research have been concentrated on finding new and practical strategies for employing benzimidazole‐based compounds. This review focuses on the latest advancements and methodologies for exploiting various benzimidazole‐bearing compounds for the treatment of varied sorts of cancer, considering the mechanism of their function against cancer cell lines.

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SAR investigation and optimization of benzimidazole-based derivatives as antimicrobial agents against Gram-negative bacteria

Cited by 10 publications

References 79 publications

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors

Molecular Docking Investigation and Pharmacokinetic Properties Prediction of Some Benzimidazole Analogues as Dihydropteroate Synthase (DHPS) Inhibitors

Recent Advances in the Anticancer Applications of Benzimidazole Derivatives

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