Effect of amino acids and amines on the activity of the recombinant ι-carbonic anhydrase from the Gram-negative bacterium <i>Burkholderia territorii</i>

Luca, Viviana De; Petreni, Andrea; Carginale, Vincenzo; Scaloni, Andrea; Supuran, Claudiu T.; Capasso, Clemente

doi:10.1080/14756366.2021.1919891

Cited by 9 publications

(3 citation statements)

References 73 publications

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“…CAs of interest were produced in E. coli (DE3) competent cells through the suitable vector expression and, then, purified, as previously reported 61 .…”

Section: Methodsmentioning

confidence: 99%

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

D’Agostino

Mathew²,

Angelini

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs ( 1–9 ) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9 , highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

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“…CAs of interest were produced in E. coli (DE3) competent cells through the suitable vector expression and, then, purified, as previously reported 61 .…”

Section: Methodsmentioning

confidence: 99%

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

D’Agostino

Mathew²,

Angelini

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…[15][16][17] SN derivatives are an important class of drugs used in clinics as pharmacological agents such as anti-bacterial, anti-tumor, anti-thyroid, anti-fungal, anti-inflammatory, anti-obesity, etc. [18] Recent use of SNs includes anti-cancer, antiviral HIV (HIV protease inhibitors, non-nucleoside HIV reverse transcriptase or HIV integrase inhibitors), [19][20][21] and Alzheimer's disease [22] agents. Such properties of SN drugs are likely due to the presence of -SO 2 NH-(or -OSO 2 NH-, -NHSO 2 NH-) moieties which can react with metal ions or bio-macromolecules like amino acid residues in proteins and DNA or RNA acting as drug targets.…”

Section: Introductionmentioning

confidence: 99%

Lysozyme binding with sulfa group of antibiotics: Comparative binding thermodynamics and computational study

2022

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Protein-drug binding study addresses a broad domain of biological problems associating molecular functions to physiological processes composing and modifying safe and coherent drug therapeutics. Comparison of the binding and thermodynamic aspect of sulfa drugs, sulfamethazine (SMZ) and sulfadiazine (SDZ) with the protein, lysozyme (Lyz) was carried out using spectroscopic, molecular docking, and dynamic simulation studies. The fluorescence quenching and apparent binding constant for the binding reaction were calculated to be in the order of 10 4 M À1 , slightly higher for SMZ as compared to that of SDZ and the binding stoichiometry values show 1:1 drug binding with each protein molecule. The binding was an enthalpy-driven spontaneous exothermic reaction favored by a negative enthalpy and a positive entropy contribution for both the complexes. The binding from the fluorescence quenching data suggests a static quenching mechanism dominated by non-polyelectrolytic components. Synchronous fluorescence denoted a conformational change in the tryptophan moiety of the protein. Molecular docking and dynamic simulation study provided a clearer view of the interaction pattern, where the drug resides on the binding pocket of the protein structure. Overall the protein, Lyz binding of SMZ was slightly more favored over SDZ.

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“…In contrast, the β- or γ-classes which are localised in the cytoplasm, perform intracellular functions, such as CO 2 /HCO 3 – transport/homeostasis and pH regulation 7 . Recently, in some Gram-negative bacteria lacking α-CAs, it has been discovered the presence of β-, γ-, and ι-CAs with a potential signal peptide at their N-terminus, which probably may have a function similar to that performed by α-CAs in the species where this class is present 10 , 11 , 13–16 . The function of CAs in bacteria and how these enzymes influence the bacterial lifecycle have been recently examined in the literature.…”

Section: Introductionmentioning

confidence: 99%

The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth

Luca

Carginale

Supuran

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrases, catalysing the reversible CO 2 hydration reaction, contribute in all living organisms to the maintenance of stable metabolic functions depending on intracellular concentrations of carbon dioxide, bicarbonate, and protons. Recent studies have examined how CAs affect bacterial lifecycle, considering these enzymes druggable targets due to interference with their activities by using inhibitors or activators. Here, we propose Escherichia coli cells as a model for testing the effect of acetazolamide (AZA), a potent CA inhibitor, on bacterial survival by evaluating E. coli growth through its glucose consumption. AZA, at concentrations higher than 31.2 µg/mL, was able to impair E. coli growth and glucose uptake. AZA is a good inhibitor of the two recombinant E. coli CAs, the β-CA CynT2, and the γ-CA EcoCAγ, with KIs of 227 and 248 nM, respectively. This study provides a proof-of-concept, low-cost method for identifying effective CA inhibitors capable of impairing bacterial metabolism.

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Effect of amino acids and amines on the activity of the recombinant ι-carbonic anhydrase from the Gram-negative bacterium Burkholderia territorii

Cited by 9 publications

References 73 publications

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

Lysozyme binding with sulfa group of antibiotics: Comparative binding thermodynamics and computational study

The gram-negative bacterium Escherichia coli as a model for testing the effect of carbonic anhydrase inhibition on bacterial growth

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