Novel copper complexes of metronidazole and metronidazole benzoate: synthesis, characterization, biological and computational studies

Rafique, Bushra; Shafique, Kainat; Hamid, Sabahat; Kalsoom, Saima; Hashim, Muhammad; Mirza, Bushra; Jafri, Laila; Iqbal, Mudassir

doi:10.1080/07391102.2020.1871072

Cited by 13 publications

(7 citation statements)

References 42 publications

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“…In the light of this information, the inhibition effects of methyl 4‐aminobenzoate derivatives on GST and GR activities, which are active in the GSH system, were investigated in our study. It was reported that methyl benzoate derivatives had high inhibitory effects on some metabolic enzymes such as human erythrocyte glucose 6‐phosphate dehydrogenase (G6PD), 6‐phosphogluconate dehydrogenase (6PGD), human serum paraoxonase 1 (PON1) α‐amylase, and α‐glucosidase in a micro molar range [39–41] …”

Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Korkmaz¹,

Güller²,

Kalın³

et al. 2023

Chemistry & Biodiversity

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A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S‐transferase (GST) are two glutathione‐related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4‐aminobenzoate derivatives on GR and GST were examined in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4‐amino‐3‐bromo‐5‐fluorobenzoate with Ki value of 0.325±0.012 μM) and compound 5 (methyl 4‐amino‐2‐nitrobenzoate with Ki value of 92.41±22.26 μM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer‐aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4‐amino‐2‐bromobenzoate) and 6 (methyl 4‐amino‐2‐chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies.

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Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Korkmaz¹,

Güller²,

Kalın³

et al. 2023

Chemistry & Biodiversity

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“…The glucose adsorption activity of SAE−CS−TPP at lower glucose concentrations (5, 20 mM), might decrease the glucose that is accessible to transports via the intestinal lumen, resulting in a reduction of postprandial glucose level in vivo [45] . According to the literature, the copper complexes of metronidazole and metronidazole benzoate have shown significant α‐amylase and α‐glucosidase inhibitory activity [46] . Considering the above characteristic feature, it was assumed that the metronidazole may contribute to the glucose adsorption process as well.…”

Section: Resultsmentioning

confidence: 99%

“…[45] According to the literature, the copper complexes of metronidazole and metronidazole benzoate have shown significant α-amylase and α-glucosidase inhibitory activity. [46] Considering the above characteristic feature, it was assumed that the metronidazole may contribute to the glucose adsorption process as well. Therefore, metronidazole was used as the reference compound in this assay which demonstrated a concentration-dependent glucose adsorption activity.…”

Section: Glucose Adsorption Activitymentioning

confidence: 99%

Development, Characterization, in vitro Antidiabetic Activity of Chitosan−tripolyphosphate Nanoparticles Encapsulating Gmelina arborea Roxb. and Spondias pinnata (L.f) Kurz Aqueous Extracts

Wadasinghe,

Kalansuriya,

Attanayake

2023

ChemistrySelect

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Nanoencapsulation is a promising strategy for the development of novel therapeutic agents from crude aqueous extracts derived from Gmelina arborea Roxb. and Spondias pinnata (L.f) Kurz stem bark against type 2 diabetes mellitus. In this study, G. arborea and S. pinnata aqueous extracts encapsulated chitosan−tripolyphosphate nanoparticles (GAE−CS−TPP, SAE−CS−TPP) were prepared following the ionic gelation method and were characterized via various methods. The prepared nanoparticles were evaluated for their in vitro antidiabetic activity following the reported procedures. The antidiabetic potential of the GAE−CS−TPP and SAE−CS−TPP nanoparticles were evaluated against α‐amylase, α‐glucosidase, DPP‐IV enzymes, glucose uptake, and glucose adsorption assays. SEM analysis revealed that the GAE−CS−TPP and SAE−CS−TPP were spherical‐shaped with an average diameter of 138±30 nm and 129±19 nm respectively. The encapsulation efficiencies and the loading capacities of GAE−CS−TPP and SAE−CS−TPP were (57.64±2.38 % and 0.25±0.07 %) and (68.21±0.66 % and 0.79±0.17 %) respectively. The α‐glucosidase, DPP‐IV enzyme inhibitory activities (8.09±0.99 and 7.95±0.68 mg/mL,) of GAE−CS−TPP nanoparticles were more potent than that of G. arborea aqueous extract by 3.89 and 3.12 folds respectively. In conclusion, GAE−CS−TPP and SAE−CS−TPP nanoparticles exert antidiabetic activity to be used in pharmaceutical formulations to combat hyperglycemia in diabetes.

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“…Cu 2+ binds through imidazole nitrogen and the forms complex [Cu(L16) 2 Cl(H 2 0)] 2 Cl 2 , with higher stability, protected from inactivation by numerous enzymes [ 86 ]. A study published in 2022 pointed out that copper complexes with metronidazole or metronidazole benzoate have overall better biological activity compared to each ligand used alone [ 87 ].…”

Section: Copper Interactions With Antibioticsmentioning

confidence: 99%

The Impact of Copper Ions on the Activity of Antibiotic Drugs

2023

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Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu–antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu–antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.

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Novel copper complexes of metronidazole and metronidazole benzoate: synthesis, characterization, biological and computational studies

Cited by 13 publications

References 42 publications

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Development, Characterization, in vitro Antidiabetic Activity of Chitosan−tripolyphosphate Nanoparticles Encapsulating Gmelina arborea Roxb. and Spondias pinnata (L.f) Kurz Aqueous Extracts

The Impact of Copper Ions on the Activity of Antibiotic Drugs

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