Famotidine, an Antiulcer Agent, Strongly Inhibits <i>Helicobacter pylori</i> and Human Carbonic Anhydrases

Angeli, Andrea; Ferraroni, Marta; Supuran, Claudiu T.

doi:10.1021/acsmedchemlett.8b00334

Cited by 48 publications

(33 citation statements)

References 21 publications

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“…Datasets were processed automatically with the xia2 expert system (https://xia2.github.io/index.html) and scaled with Aimless [54]. The space group resulted in being isomorphous with the native apo hCA I and the structure of hCA I in a complex with the inhibitor famotidine (PDB ID 6g3v) was used as a starting points for the refinement [55]. The structure was refined using the software package Phenix [56].…”

Section: Crystallization Data Collection and Structure Determinationmentioning

confidence: 99%

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

Ali

Bozdağ

Farooq

et al. 2020

IJMS

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A drug design strategy of carbonic anhydrase inhibitors (CAIs) belonging to sulfonamides incorporating ureidoethylaminobenzyl tails is presented. A variety of substitution patterns on the ring and the tails, located on paraor metapositions with respect to the sulfonamide warheads were incorporated in the new compounds. Inhibition of human carbonic anhydrases (hCA) isoforms I, II, IX and XII, involving various pathologies, was assessed with the new compounds. Selective inhibitory profile towards hCA II was observed, the most active compounds being low nM inhibitors (K I s of 2.8-9.2 nM, respectively). Extensive X-ray crystallographic analysis of several sulfonamides in an adduct with hCA I allowed an in-depth understanding of their binding mode and to lay a detailed structure-activity relationship.

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Section: Crystallization Data Collection and Structure Determinationmentioning

confidence: 99%

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

Ali

Bozdağ

Farooq

et al. 2020

IJMS

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“…The k cat value of the recombinant MreCA resulted in one order higher than those calculated for the other fungal CAs [24,32,34,38], as well as for the human isoform, hCA I (α-CA) [39,40]. Moreover, it was more active than the homologous MgCA enzyme.…”

Section: Integrity Of the Target Enzymementioning

confidence: 77%

“…Table 3 includes the inhibition data of the two fungal enzymes, MreCA and MgCA [24]. Mainly, for comparison reasons, the data of the sulfonamide inhibition profiles of the two human isoforms, hCA I and hCA II, have also been added [39,40]. The following results can be observed from the data of Table 3: 1.…”

Section: Sulfonamide Inhibition Profilementioning

confidence: 99%

Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions

et al. 2020

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The critical CO2 hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO2 and HCO3− at the cellular level, which will not be ensured by the low velocity of the uncatalyzed reaction. CA inhibition may impair the growth of microorganisms. In the yeasts, Candida albicans and Malassezia globosa, the activity of the unique β-CA identified in their genomes was demonstrated to be essential for growth of the pathogen. Here, we decided to investigate the sulfonamide inhibition profile of the homologous β-CA (MreCA) identified in the genome of Malassezia restricta, an opportunistic pathogen triggering dandruff and seborrheic dermatitis. Among 40 investigated derivatives, the best MreCA sulfonamide inhibitors were dorzolamide, brinzolamide, indisulam, valdecoxib, sulthiam, and acetazolamide (KI < 1.0 μM). The MreCA inhibition profile was different from those of the homologous enzyme from Malassezia globosa (MgCA) and the human isoenzymes (hCA I and hCA II). These results might be useful to for designing CA inhibitor scaffolds that may selectively inhibit the dandruff-producing fungi.

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“…from the resistance to the existing antimicrobial medicines is one of the most severe problems afflicting the human community. Table 2 reports the inhibition profile of EcoCAc, which was compared with the inhibitory behaviour of hCA I, hCA II, and VchCAc reported earlier by our group 17,56,71 . From the data of The behaviour of EcoCAc is somewhat challenging to explain observing the different inhibition profiles and comparing them to the orthologous VchCAc and the two human isoforms (hCA I and hCA II).…”

Section: Sulphonamide Inhibition Profilementioning

confidence: 99%

Escherichia coli γ-carbonic anhydrase: characterisation and effects of simple aromatic/heterocyclic sulphonamide inhibitors

Prete

Bua

Supuran

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes involved in biosynthetic processes, transport, supply, and balance of CO 2 /HCO 3 into the cell. In Bacteria, CAs avoid the depletion of the dissolved CO 2 /HCO 3 from the cell, providing them to the central metabolism that is compromised without the CA activity. The involvement of CAs in the survival, pathogenicity, and virulence of several bacterial pathogenic species is recent. Here, we report the kinetic properties of the recombinant c-CA (EcoCAc) encoded in the genome of Escherichia coli. EcoCAc is an excellent catalyst for the physiological CO 2 hydration reaction to bicarbonate and protons, with a k cat of 5.7 Â 10 5 s À1 and k cat /K M of 6.9 Â 10 6 M À1 s À1. The EcoCAc inhibition profile with a broad series of known CA inhibitors, the substituted benzene-sulphonamides, and clinically licenced drugs was explored. Benzolamide showed a K I lower than 100 nM. Our study reinforces the hypothesis that the synthesis of new drugs capable of interfering selectively with the bacterial CA activity, avoiding the inhibition of the human a-CAs, is achievable and may lead to novel antibacterials.

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Famotidine, an Antiulcer Agent, Strongly Inhibits Helicobacter pylori and Human Carbonic Anhydrases

Cited by 48 publications

References 21 publications

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions

Escherichia coli γ-carbonic anhydrase: characterisation and effects of simple aromatic/heterocyclic sulphonamide inhibitors

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