Inhibition of the α-carbonic anhydrase from<i>Vibrio cholerae</i>with amides and sulfonamides incorporating imidazole moieties

Vita, Daniela De; Angeli, Andrea; Pandolfi, Fabiana; Bortolami, Martina; Costi, Roberta; Santo, Roberto Di; Suffredini, Elisabetta; Ceruso, Mariangela; Prete, Sonia Del; Capasso, Clemente; Scipione, Luigi

doi:10.1080/14756366.2017.1327522

Cited by 35 publications

(17 citation statements)

References 39 publications

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“…Sulfonamides 3a – 3l were tested as inhibitors of four hCAs involved in various pathologies, hCA I, II, VII, and IX, as well as three β- and γ-CAs from pathogenic organisms: the β-CAs from the bacterium Vibrio cholerae (VchCAβ) and the fungus Malassezia globosa (MgCA), and the γ-CA from the same pathogenic bacterium, VchCAγ–enzymes recently cloned and characterized by our group as potential anti-infective targets [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The inhibition constants were obtained by non-linear least-squares methods using PRISM 3 and the Cheng-Prusoff equation, as reported earlier [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. All CAs were recombinant proteins produced as reported earlier by our groups [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

Section: Methodsmentioning

confidence: 99%

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Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors

et al. 2018

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A series of benzamides incorporating 4-sulfamoyl moieties were obtained by reacting 4-sulfamoyl benzoic acid with primary and secondary amines and amino acids. These sulfonamides were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human (h) isoforms hCA II, VII, and IX were inhibited in the low nanomolar or subnanomolar ranges, whereas hCA I was slightly less sensitive to inhibition (KIs of 5.3–334 nM). The β- and γ-class CAs from pathogenic bacteria and fungi, such as Vibrio cholerae and Malassezia globosa, were inhibited in the micromolar range by the sulfonamides reported in the paper. The benzamide-4-sulfonamides are a promising class of highly effective CA inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors

et al. 2018

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“…Enzyme and inhibitor solutions were pre-incubated together for 15 min (standard assay at room temperature) prior to assay, in order to allow for the formation of the enzyme-inhibitor complex. The inhibition constants were obtained by non-linear least-squares methods using PRISM 3 and the Cheng-Prusoff equation, as reported earlier 14 , 16–22 . All CAs were recombinant proteins produced as reported earlier by our groups 16–22 .…”

Section: Methodsmentioning

confidence: 99%

Inhibition of α-, β-, γ-, and δ-carbonic anhydrases from bacteria and diatoms withN′-aryl-N-hydroxy-ureas

Berrino

Bozdağ

Prete

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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The inhibition of α-, β-, γ-, and δ-class carbonic anhydrases (CAs, EC 4.2.1.1) from bacteria (Vibrio cholerae and Porphyromonas gingivalis) and diatoms (Thalassiosira weissflogii) with a panel of N’-aryl-N-hydroxy-ureas is reported. The α-/β-CAs from V. cholerae (VchCAα and VchCAβ) were effectively inhibited by some of these derivatives, with KIs in the range of 97.5 nM – 7.26 µM and 52.5 nM – 1.81 µM, respectively, whereas the γ-class enzyme VchCAγ was less sensitive to inhibition (KIs of 4.75 – 8.87 µM). The β-CA from the pathogenic bacterium Porphyromonas gingivalis (PgiCAβ) was not inhibited by these compounds (KIs > 10 µM) whereas the corresponding γ-class enzyme (PgiCAγ) was effectively inhibited (KIs of 59.8 nM – 6.42 µM). The δ-CA from the diatom Thalassiosira weissflogii (TweCAδ) showed effective inhibition with these derivatives (KIs of 33.3 nM – 8.74 µM). As most of these N-hydroxyureas are also ineffective as inhibitors of the human (h) widespread isoforms hCA I and II (KIs > 10 µM), this class of derivatives may lead to the development of CA inhibitors selective for bacterial/diatom enzymes over their human counterparts and thus to anti-infectives or agents with environmental applications.

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“…The inhibition constants were obtained by non-linear least-squares methods using PRISM 3 and the Cheng–Prusoff equation, as reported earlier 10 , 49 . All CAs were recombinant proteins produced as reported earlier by our groups 50–53 .…”

Section: Methodsmentioning

confidence: 99%

Discovering a new class of antifungal agents that selectively inhibits microbial carbonic anhydrases

Annunziato

Giovati

Angeli

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Infections caused by pathogens resistant to the available antimicrobial treatments represent nowadays a threat to global public health. Recently, it has been demonstrated that carbonic anhydrases (CAs) are essential for the growth of many pathogens and their inhibition leads to growth defects. Principal drawbacks in using CA inhibitors (CAIs) as antimicrobial agents are the side effects due to the lack of selectivity toward human CA isoforms. Herein we report a new class of CAIs, which preferentially interacts with microbial CA active sites over the human ones. The mechanism of action of these inhibitors was investigated against an important fungal pathogen, Cryptococcus neoformans, revealing that they are also able to inhibit CA in microbial cells growing in vitro. At our best knowledge, this is the first report on newly designed synthetic compounds selectively targeting β-CAs and provides a proof of concept of microbial CAs suitability as an antimicrobial drug target.

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Inhibition of the α-carbonic anhydrase fromVibrio choleraewith amides and sulfonamides incorporating imidazole moieties

Cited by 35 publications

References 39 publications

Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors

Benzamide-4-Sulfonamides Are Effective Human Carbonic Anhydrase I, II, VII, and IX Inhibitors

Inhibition of α-, β-, γ-, and δ-carbonic anhydrases from bacteria and diatoms withN′-aryl-N-hydroxy-ureas

Discovering a new class of antifungal agents that selectively inhibits microbial carbonic anhydrases

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