Synthesis, antimicrobial, antiquorum-sensing and antitumor activities of new benzimidazole analogs

El‐Gohary, Nadia S.; Shaaban, Mona I.

doi:10.1016/j.ejmech.2017.05.064

Cited by 64 publications

(22 citation statements)

References 48 publications

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“…Particularly,a ltera-tions in the conserved ParC helix a4 residues of the topoisomerase IV-DNA complex, positioned in close proximity to the groups at the N1 positiono fq uinolones, directly weakened the binding affinity between quinolonea ntimicrobials and target enzymes. [17][18][19] Benzimidazole derivatives couldi nteract with DNA from different microbial strains or inhibitt he biosynthesis of essential ergosterol in the membrane of fungi and protozoa to exhibit antimicrobial activity. [14][15][16] Benzimidazole, with al arge, conjugated, rigid, planar structure, is structurallys imilart op urine nucleoside bases,a nd has been attracting increasing interest in drug design for the development of potentiala ntimicrobiala gents.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16] Benzimidazole, with al arge, conjugated, rigid, planar structure, is structurallys imilart op urine nucleoside bases,a nd has been attracting increasing interest in drug design for the development of potentiala ntimicrobiala gents. [17][18][19] Benzimidazole derivatives couldi nteract with DNA from different microbial strains or inhibitt he biosynthesis of essential ergosterol in the membrane of fungi and protozoa to exhibit antimicrobial activity. [20,21] Previous studies reported that some benzimidazole-based hybrids, such as sulfonamides, 5-fluorouracils, and naphthalimides, exhibitedg ood antimicrobiala ctivities and a broad antibacterial spectrum.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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A series of benzimidazole-quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2-fluorobenzyl derivative 5 b (ethyl 7-chloro-6-fluoro-1-[[1-[(2-fluorophenyl)methyl]benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep-2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV-DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug-resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

et al. 2018

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“…The benzimidazole family of heterocyclic compounds has received considerable attention as bioactive compounds. They are associated with a range of biological activities such as antimalarial 16 , antimicrobial 17 , antiviral 18 , antiprotozoal 19 , antiinflammatory 20 , anti-hypertensive 21 and anti-tumour 22,23 activities. They are structural isosteres of purine nucleic acids and can potentially interact with biological macromolecules such as protein, enzymes and receptors 24 .…”

Section: Plasmepsin Inhibitors Have Been Shown To Killmentioning

confidence: 99%

Synthesis, Characterization and Biological Evaluation of Benzimidazole - Dihydroartemisinin Hybrids as Potential Dual Acting Antimalarial Agents

2019

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Malaria is a parasitic disease caused by various species of the Plasmodium parasite. In 2016, there were about 216 million cases resulting in 445,000 deaths, with sub-saharan Africa bearing the heaviest burden of the disease. The currently recommended treatment for malariaÂ are combination therapies containing Artemisinin (ACTâ€™s). However, the effectiveness of the Artemisinins is being compromised by the emergence of resistance to the drug and this amplifies the need for new antimalarial drugs. The Benzimidazole scaffold is one of the privileged structures in medicinal chemistry and is associated with a number of biological activities including antimalarial activity which may be through inhibition of the Plasmodial plasmepsin II enzyme. The present study utilizes the concept of molecular hybridization to synthesize hybrid compounds that contain two pharmacophores, acting through two distinct mechanisms. The aim is to improve efficacy and possibly prevent or slow down the emergence of parasite resistance. To confirm their structures, the conjugates were purified by chromatography and characterized using Nuclear Magnetic Resonance (NMR), Mass spectrometry and Infra-red spectroscopy. Antimalarial activities of the hybrids were evaluated in-vitro against the 3D7 strain of Plasmodium falciparum using the parasite Lactate dehydrogenase assay. The hybrids were successfully synthesized with yields ranging from 63.48 percent to 67.60 percent and were all active against the parasite. The Mebendazole conjugate of dihydroartemisinin showed the highest activity with IC50 of 6.861 nM and 6.967 nM for the 5-Benzimidazolecarboxylic acid conjugate of dihydroartemisinin. All the compounds showed statistically significant (p < 0.05) increase in activity as compared to Dihydroartemisinin and Chloroquine alone. These hybrid compounds with improved physicochemical and pharmacological properties may serve as templates for the development of a new class of anitmalarial drugs, which possess advantages over existing drugs in terms of effectiveness and also the ability to overcome the problem of resistance during malaria chemotherapy.

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“…Among these currently marketed benzimidazole drugs to treat several diseases, we can mention bendamustine, selumetinib, galeterone, and pracinostat as antitumor agents; pantoprazole, lansoprazole, esomeprazole, and ilaprazole as proton pump inhibitors; bezitramide as an analgesic; mebendazole, albendazole, thiabendazole, and flubendazole as antihelminthics; ridinilazole as antibacterial; astemizole and bilastine as antihistamines; enviradine, samatasvir, and maribavir as antivirals; and candesartan and mibefradil as antihypertensive [1,[4][5][6][7]. Recent research recommends benzimidazole derivatives as potential EGFR and erbB2 inhibitors [8,9], DNA/RNA binding ligands [10,11], antitumor agents [12][13][14], anti-Alzheimer agents [15,16], antidiabetic agents [17,18], antiparasitic agents [10,19], antimicrobial agents [20,21], antiquorum-sensing agents [12], and antimalarial agents [19]. Intensive studies have demonstrated the use of the benzimidazole scaffold as key pharmacophore in clinically approved analgesic and anti-inflammatory agents [22].…”

Section: Introductionmentioning

confidence: 99%

Introductory Chapter: Short Insight in Synthesis and Applications of Benzimidazole and Its Derivatives

Marinescu¹

2019

Chemistry and Applications of Benzimidazole and Its Derivatives

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Synthesis, antimicrobial, antiquorum-sensing and antitumor activities of new benzimidazole analogs

Cited by 64 publications

References 48 publications

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA

Synthesis, Characterization and Biological Evaluation of Benzimidazole - Dihydroartemisinin Hybrids as Potential Dual Acting Antimalarial Agents

Introductory Chapter: Short Insight in Synthesis and Applications of Benzimidazole and Its Derivatives

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