Metronidazole-conjugates: A comprehensive review of recent developments towards synthesis and medicinal perspective

Patel, Om Prakash; Jesumoroti, Omobolanle J.; Legoabe, Lesetja J.; Beteck, Richard M.

doi:10.1016/j.ejmech.2020.112994

Cited by 17 publications

(10 citation statements)

References 131 publications

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“…It can act as antimicrobial [1], antiprotozoal [2], antiviral [3], antileishmanial [4], antigiardial [5], antioxidant [6], anti-inflammatory [7], antiplasmodial and antimycobacterial [8]. Regularly, besides the mentioned applications, MET is highly indicated for the treatment of infections caused by drug-resistant bacteria (anaerobic Grampositive and Gram-negative bacteria), tuberculosis, protozoan infections (trichomoniasis, amoebiasis, bacterial vaginosis, giardiasis, non-gonococcal urethritis) and visceral leishmaniasis [9]. Its mechanisms of actions can be explained due to the nitro group reduction of anaerobic organisms, inhibiting the nucleic acid synthesis by DNA strand break [10].…”

Section: Introductionmentioning

confidence: 99%

Silver nanoparticles effect on drug release of metronidazole in natural rubber latex dressing

et al. 2021

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Natural rubber latex (NRL) from Hevea brasiliensis has shown great potential for dermal applications due to its angiogenesis capacity and biocompatibility. Metronidazole (MET) is a synthetic antibiotic used to treat various infections. However, this drug reports dangerous effects when high concentrations are administered. In this study, we used silver nanoparticles (AgNPs) in order to minimize these toxicological effects. For this, the membranes were characterized by physicochemical, molecular modeling, in vitro release and hemocompatibility assays. In the release assays, 14.25% of the MET and 27.28% of the AgNP + MET complex were released simultaneously, indicating that these nanoparticles work as drug carriers. Molecular modeling simulation helped to explain the in vitro release results, showing that AgNPs can interact more efficiently with MET molecules. Moreover, similarities in reactivity between NRL and MET suggested that some drug molecules may remain in the matrix during the release process. The membranes did not present significant hemolytic activity after 24 h of incubation. These results demonstrated that the NRL + AgNP + MET membrane can be used as a dressing in the treatment of infectious processes.

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Section: Introductionmentioning

confidence: 99%

Silver nanoparticles effect on drug release of metronidazole in natural rubber latex dressing

et al. 2021

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“…[52] Although 1 has shown antimicrobial activity toward a range of organisms, to our knowledge it has not been applied toward Streptococcus pneumoniae growth. [53,54] S. pneumoniae is a common opportunistic pathogenic microbe that is the leading cause of community acquired bacterial pneumonia. Bacterial pneumonia unequally targets people with compromised immune systems including children and the elderly.…”

Section: Resultsmentioning

confidence: 99%

Cu‐Catalyzed Chan–Evans–Lam Coupling Reactions of 2‐Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S. pneumoniae

Raju

Sheridan

Hauer

et al. 2022

Chemistry & Biodiversity

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The coupling of phenylboronic acids with poorly-activated imidazoles is studied as a model system to explore the use of copper-catalyzed Chan -Evans-Lam (CEL) coupling for targeted CÀ N bond forming reactions. Optimized CEL reaction conditions are reported for four phenanthroline-based ligand systems, where the ligand 4,5-diazafluoren-9-one (dafo, L2) with 1 molar equivalent of potassium carbonate yielded the highest reactivity. The substrate 2-nitroimidazole (also known as azomycin) has documented antimicrobial activity against a range of microbes. Here N-arylation of 2-nitroimidazole with a range of aryl boronic acids has been successfully developed by copper(II)-catalyzed CEL reactions. Azomycin and a range of newly arylated azomycin derivatives were screened against S. pneumoniae, where 1-(4-(benzyloxy)phenyl)-2-nitro-1H-imidazole (3d) was demonstrated to have a minimal inhibition concentration value of 3.3 μg/mL.

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“…The underlying factor for treatment failure is resistance by biofilms that form a protective shield to reduce the penetration of metronidazole (Ma et al, 2020). Leaving the essential nitroimidazole moiety intact, conjugates of metronidazole (Patel et al, 2021), via N 1 -alkyl or 2-methyl linker or both, with different structural nuclei such as thiomorpholine-1,1-dioxide, have resulted in hybrids with superior activity against metronidazole sensitive as well as resistant H. pylori strains (Rossi and Ciofalo, 2020). Accordingly, the pharmacophore of metronidazole, a 5-nitroimidazole motif, was conjugated with rifamycin, an established agent against biofilm-forming pathogens.…”

Section: Synthesis Of Tnp-2092mentioning

confidence: 99%

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates

Surur

Sun

2021

Front. Chem.

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The tale of abate in antibiotics continued defense mechanisms that chaperone the rise of drug-defying superbugs—on the other hand, the astray in antibacterial drug discovery and development. Our salvation lies in circumventing the genesis of resistance. Considering the competitive advantages of antibacterial chemotherapeutic agents equipped with multiple warheads against resistance, the development of hybrids has rejuvenated. The adoption of antibiotic hybrid paradigm to macrocycles has advanced novel chemical entities to clinical trials. The multi-targeted TD-1792, for instance, retained potent antibacterial activities against multiple strains that are resistant to its constituent, vancomycin. Moreover, the antibiotic conjugation of rifamycins has provided hybrid clinical candidates with desirable efficacy and safety profiles. In 2020, the U.S. FDA has granted an orphan drug designation to TNP-2092, a conjugate of rifamycin and fluoroquinolone, for the treatment of prosthetic joint infections. DSTA4637S is a pioneer antibacterial agent under clinical development and represents a novel class of bacterial therapy, that is, antibody–antibiotic conjugates. DSTA4637S is effective against the notorious persistent S. aureus bacteremia, a revelation of the abracadabra potential of antibiotic hybrid approaches.

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Metronidazole-conjugates: A comprehensive review of recent developments towards synthesis and medicinal perspective

Cited by 17 publications

References 131 publications

Silver nanoparticles effect on drug release of metronidazole in natural rubber latex dressing

Silver nanoparticles effect on drug release of metronidazole in natural rubber latex dressing

Cu‐Catalyzed Chan–Evans–Lam Coupling Reactions of 2‐Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S. pneumoniae

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates

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