Fungal Carbonic Anhydrases and Their Inhibition

Lehneck, Ronny; Pöggeler, Stefanie

doi:10.1007/7355_2016_10

Cited by 4 publications

(12 citation statements)

References 90 publications

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“…Fungal CAs are of great interest both for biotechnological and pharmaceutical applications [10] because some of these enzymes are stable, relatively easy to produce, and may be used as model enzymes for testing inhibitors/activators. The organism Sordaria macrospora, used as a genetic model to study fruiting body development of filamentous fungi, encodes for at least four different CAs, two of which were thoroughly investigated earlier, CAS1 and CAS2.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The CA metalloenzymes are ubiquitous in most life forms, with eight distinct genetic families encoding the α-, β-, γ-, δ-, ζ-, η-, θ-, and ι-CAs [7][8][9][10][11][12][13]. By catalyzing the hydration of CO 2 to bicarbonate and protons, CAs are involved in various processes, starting with pH regulation and ending with metabolism [4,[7][8][9][10][11][12][13]. In fungi, they play crucial roles in growth, development, virulence, and survival [10,11], and modulation of their activity with inhibitors and/or activators was proposed as a new approach for designing antifungals [10,11,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…By catalyzing the hydration of CO 2 to bicarbonate and protons, CAs are involved in various processes, starting with pH regulation and ending with metabolism [4,[7][8][9][10][11][12][13]. In fungi, they play crucial roles in growth, development, virulence, and survival [10,11], and modulation of their activity with inhibitors and/or activators was proposed as a new approach for designing antifungals [10,11,[14][15][16]. The metal ion from the enzyme active site is usually coordinated by three amino-acid residues, whereas the fourth ligand is a water molecule or hydroxide ion which acts as a nucleophile in the hydrolytic reactions [4,[7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…In fungi, they play crucial roles in growth, development, virulence, and survival [10,11], and modulation of their activity with inhibitors and/or activators was proposed as a new approach for designing antifungals [10,11,[14][15][16]. The metal ion from the enzyme active site is usually coordinated by three amino-acid residues, whereas the fourth ligand is a water molecule or hydroxide ion which acts as a nucleophile in the hydrolytic reactions [4,[7][8][9][10][11][12][13]. In β-CAs the Zn(II) is coordinated by two Cys residues, one His residue, and one water molecule/hydroxide ion [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora

et al. 2020

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A new β-class carbonic anhydrase was cloned and purified from the filamentous ascomycete Sordaria macrospora, CAS3. This enzyme has a higher catalytic activity compared to the other two such enzymes from this fungus, CAS1 and CAS2, which were reported earlier, with the following kinetic parameters: kcat of (7.9 ± 0.2) × 105 s−1, and kcat/Km of (9.5 ± 0.12) × 107 M−1∙s−1. An inhibition study with a panel of sulfonamides and one sulfamate was also performed. The most effective CAS3 inhibitors were benzolamide, brinzolamide, dichlorophnamide, methazolamide, acetazolamide, ethoxzolamide, sulfanilamide, methanilamide, and benzene-1,3-disulfonamide, with KIs in the range of 54–95 nM. CAS3 generally shows a higher affinity for this class of inhibitors compared to CAS1 and CAS2. As S. macrospora is a model organism for the study of fruiting body development in fungi, these data may be useful for developing antifungal compounds based on CA inhibition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora

et al. 2020

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Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors ofcandidaβ-carbonic anhydrase enzyme

Akdemir

Angeli

Göktaş

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1 H -indole-2,3-dione 3-[ N -(4-sulfamoylphenyl)thiosemicarbazones] 4a–m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (K I of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies.

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Perspectives on the specific targeting of Fusarium graminearum for the development of alternative head blight treatment approaches

et al. 2017

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Diseases of agricultural crops caused by fungi have devastating economic and health effects. Fusarium head blight (FHB) is one of the most damaging diseases of wheat and other small grain cereals. FHB reduces agricultural yield while also affecting food supply and safety through deposition of toxins (mycotoxins/phytotoxins). Control of FHB growth and toxin accumulation in grains remain major challenges. While the ultimate goal in the battle against FHB is the development of resistant wheat varieties, the actual use of fully resistant plants that preclude any need for treatment with fungicides remains out of sight. Current antifungals being applied against FHB are generally azole-based inhibitors. However, usage of these azole-based fungicides is being complicated by the facts that these are active only during specific short-lived developmental time periods, fungi are developing increased resistance to them and they are having significant environmental impacts. As such, there is a great need for more targeted, specific and effective antifungal agents to address the significant threat of FHB. This review provides an overview of some of the more promising fungal targets that are currently being investigated for antifungal development.

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Fungal Carbonic Anhydrases and Their Inhibition

Cited by 4 publications

References 90 publications

Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora

Sulfonamide Inhibition Studies of the β-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora

Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors ofcandidaβ-carbonic anhydrase enzyme

Perspectives on the specific targeting of Fusarium graminearum for the development of alternative head blight treatment approaches

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