An overview of the alpha-, beta- and gamma-carbonic anhydrases from<i>Bacteria</i>: can bacterial carbonic anhydrases shed new light on evolution of bacteria?

Capasso, Clemente; Supuran, Claudiu T.

doi:10.3109/14756366.2014.910202

Cited by 363 publications

(327 citation statements)

References 74 publications

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“…CAs distribution pattern in bacteria is very intriguing [17]. In bacteria, CAs belonging to one class, two or three different genetic families were evidenced, whereas in few of them no CAs seem to be present, i.e., Gram-negative bacteria of the genera Buchnera and Rickettsia [17]. The evolutionary relationship of CAs from pro-karyotes is thus characterized by a high degree of complexity, not entirely understood at the present time.…”

Section: Carbonic Anhydrasesmentioning

confidence: 97%

“…The *Address correspondence to these authors at the Istituto di Bioscienze e Biorisorse, CNR, via Pietro Castellino 111-80131 Napoli, Italy; Tel:/Fax: +39-081-6132559/+39-081-6132558; E-mail: clemente.capasso@ibbr.cnr.it; Laboratorio di Chimica Bioinorganica, and Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Universita` degli Studi di Firenze, via della Lastruccia 3 -50019, Sesto Fiorentino, Firenze, Italy; Tel:/Fax: +39-055-4573729/+39-055-4573005; E-mail:claudiu.supuran@unifi.it catalytic function of CO 2 hydration is maintained for all CA classes, despite the diverse spatial reorganization of the active sites [5,[11][12][13][14][15][16]. In general the catalytic efficiency of the γ-, δ-and ζ-CAs is low compared to the β-and η-CAs, which in turn are less efficient catalysts compared to many bacterial α-CAs [6,9,11,17]. Interestingly, γ-CAs use only CO 2 as substrate, while β-CAs can hydrolyze CO 2, H 2 S and COS [18].…”

Section: Carbonic Anhydrasesmentioning

confidence: 98%

“…Interestingly, γ-CAs use only CO 2 as substrate, while β-CAs can hydrolyze CO 2, H 2 S and COS [18]. Furthermore, α-CAs not only hydrate CO 2 , CS 2 but also possess esterase activity, with a range of esters of carboxylic, sulfonic or phosphate acids [6,9,11,17,19,20]. Generally, bacterial genome encodes for three CA classes that in agreement with the CA family nomenclature are designed as α, β and γ [17].…”

Section: Carbonic Anhydrasesmentioning

confidence: 99%

“…Generally, bacterial genome encodes for three CA classes that in agreement with the CA family nomenclature are designed as α, β and γ [17]. CAs distribution pattern in bacteria is very intriguing [17]. In bacteria, CAs belonging to one class, two or three different genetic families were evidenced, whereas in few of them no CAs seem to be present, i.e., Gram-negative bacteria of the genera Buchnera and Rickettsia [17].…”

Section: Carbonic Anhydrasesmentioning

confidence: 99%

“…The metal ion from the enzyme active site is coordinated by three His residues in the α-, γ-,δ-and θ-classes, by one His, and two Cys residues in β-and ζ-CAs or by two His and one Gln residues in η-class with the fourth ligand being a water molecule/hydroxide ion acting as nucleophile in the catalytic cycle of the enzyme [9,12,17,25]. The α-, β-, δ-and, probably η-and θ-CAs use Zn(II) ions at the active site, γ-CAs are Fe(II) enzymes but they are active also with bound Zn(II) or Co(II) ions, whereas ζ-class uses Cd(II) or Zn(II) to perform the physiologic reaction catalysis [6,9,12,17,26,27]. The α-, β-, γ-and ζ-CAs have been crystallized, but not δ-, η-and θ-CAs.…”

Section: Carbonic Anhydrasesmentioning

confidence: 99%

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Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Capasso

Supuran

2017

CTMC

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Background: Clinically used antibiotics act through one of these four mechanisms: cell wall biosynthesis inhibition, inhibition of protein biosynthesis, interference with DNA and RNA synthesis and the folate pathway. Objective:The metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) widespread in microorganisms and present as three genetically distinct families may be considered for the design of antiinfective agents with a different mechanism of action compared to the clinically used antibiotics. CAs are crucial for the life cycle of the pathogen, interfering with pH regulation and biosynthetic processes in which CO 2 or bicarbonate are substrates. CA inhibition was shown to lead to debilitation or growth defects of several pathogenic bacteria. Method:CAs catalyzes the interconversion between carbon dioxide to bicarbonate, leading to the formation of protons, and thus affecting pH homeostasis. Several classes of CA inhibitors (CAIs) are known to date, among which the metal complexing anions, the unsubstituted sulfonamides, the dithiocarbamates, etc., which bind to the Zn(II) ion of the enzyme either by substituting the non-protein zinc ligand or add to the metal coordination sphere.Results: Effective inhibitors for many bacterial CAs belonging to the α-, β-, and γ-CA classes were detected, some of which inhibited bacterial growth in vivo. Few of the inhibitors investigated so far were also selective for the bacterial over the human CA isoforms, which may pose problems for their wide clinical applications. Conclusion:Structure-based drug design campaigns might lead to the achievement of the desired selectivity/potency for preferentially inhibiting bacterial but not the host CAs.

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Section: Carbonic Anhydrasesmentioning

confidence: 97%

Section: Carbonic Anhydrasesmentioning

confidence: 98%

Section: Carbonic Anhydrasesmentioning

confidence: 99%

Section: Carbonic Anhydrasesmentioning

confidence: 99%

Section: Carbonic Anhydrasesmentioning

confidence: 99%

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Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Capasso

Supuran

2017

CTMC

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Exploring rhodanine linked enamine–carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies

Maddipatla,

Bakchi,

Gadhave

et al. 2024

Archiv der Pharmazie

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With the rise of multidrug‐resistant tuberculosis, the imperative for an alternative and superior treatment regimen, incorporating novel mechanisms of action, has become crucial. In pursuit of this goal, we have developed and synthesized a new series of rhodanine‐linked enamine–carbohydrazide derivatives, exploring their potential as inhibitors of mycobacterial carbonic anhydrase. The findings reveal their efficacy, displaying notable selectivity toward the mycobacterial carbonic anhydrase 2 (mtCA 2) enzyme. While exhibiting moderate activity against human carbonic anhydrase isoforms, this series demonstrates promising selectivity, positioning these compounds as potential antitubercular agents. Compound 6d was the best one from the series with a Ki value of 9.5 µM toward mtCA 2. Most of the compounds displayed moderate to good inhibition against the Mtb H37Rv strain; compound 11k showed a minimum inhibitory concentration of 1 µg/mL. Molecular docking studies revealed that compounds 6d and 11k show metal coordination with the zinc ion, like classical CA inhibitors.

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Benzothiazole derivatives in the design of antitumor agents

Paoletti,

Supuran

2024

Archiv der Pharmazie

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Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti‐inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor‐hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual‐specificity protein kinase, cyclin‐dependent protein kinases, casein kinase 2, Rho‐related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase‐2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl‐CoA desaturase, peroxisome proliferator‐activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia‐inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.

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An overview of the alpha-, beta- and gamma-carbonic anhydrases fromBacteria: can bacterial carbonic anhydrases shed new light on evolution of bacteria?

Cited by 363 publications

References 74 publications

Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Exploring rhodanine linked enamine–carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies

Benzothiazole derivatives in the design of antitumor agents

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