Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

Gawad, Nagwa M. Abdel; Amin, Noha H.; El‐Saadi, Mohammed T.; Mohamed, Fatma M.M.; Angeli, Andrea; Luca, Viviana De; Capasso, Clemente

doi:10.1016/j.bmc.2016.05.016

Cited by 55 publications

(24 citation statements)

References 82 publications

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“…In the following years, a range of analogs constituting the so-called sulfa drug class of anti-bacterials entered into clinical use, and many of these compounds are still widely used. A library of 40 compounds, 39 sulfonamides, and one sulfamate was used to provide CAIs ( Figure 8 ) [ 6 , 10 , 13 , 14 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Section: Ca Inhibitorsmentioning

confidence: 99%

“…In this context, the superfamily of carbonic anhydrases (CAs, EC 4.2.1.1) represents a valuable member of such new macromolecules affecting the growth of microorganisms or making them vulnerable to the host defense mechanisms [ 4 , 5 , 6 , 7 , 8 ]. These metalloenzymes catalyze the simple but physiologically crucial reaction of carbon dioxide hydration to bicarbonate and protons: CO 2 + H 2 O ⇄ HCO 3 − + H+ [ 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], and they are involved in the transport and supply of CO 2 or HCO 3 − in pH homeostasis, the secretion of electrolytes, biosynthetic processes, and photosynthesis [ 15 , 16 ]. Moreover, CAs are target molecules of some antibacterial drugs, such as sulfanilamide.…”

Section: Introductionmentioning

confidence: 99%

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An Overview of the Bacterial Carbonic Anhydrases

2017

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Bacteria encode carbonic anhydrases (CAs, EC 4.2.1.1) belonging to three different genetic families, the α-, β-, and γ-classes. By equilibrating CO2 and bicarbonate, these metalloenzymes interfere with pH regulation and other crucial physiological processes of these organisms. The detailed investigations of many such enzymes from pathogenic and non-pathogenic bacteria afford the opportunity to design both novel therapeutic agents, as well as biomimetic processes, for example, for CO2 capture. Investigation of bacterial CA inhibitors and activators may be relevant for finding antibiotics with a new mechanism of action.

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Section: Ca Inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Overview of the Bacterial Carbonic Anhydrases

2017

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“…A library of 40 compounds, 39 sulfonamides and one sulfamate, were used in this study ( Figure 1 ) [ 4 , 9 , 11 , 22 , 27 , 33 , 67 , 76 , 77 , 78 , 79 ]. Derivatives 1–24 and AAZ-HCT are either simple aromatic/heterocyclic sulfonamides widely used as building blocks for obtaining new families of such pharmacological agents, or they are clinically used agents, among which acetazolamide ( AAZ ), methazolamide ( MZA ), ethoxzolamide ( EZA ), and dichlorophenamide ( DCP ) are the classical, systemically acting antiglaucoma CAIs.…”

Section: Sulfonamide Inhibition Studiesmentioning

confidence: 99%

“…A serious problem associated with periodontitis is that the polymicrobial community is usually resistant to antimicrobial agents and host-defense mechanisms. In this context, we investigated the possibility of finding new anti-infectives by studying the inhibition profiles of carbonic anhydrases (CAs, EC 4.2.1.1), a superfamily of metalloenzymes which catalyze the simple but physiologically crucial reaction of carbon dioxide hydration to bicarbonate and protons: CO 2 + H 2 O ⇄ HCO 3 − + H + [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Moreover, most studies concerning the treatment of periodontitis have primarily take into account the Gram-negative bacterium Porphyromonas gingivalis because it is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Carbonic Anhydrase from Porphyromonas Gingivalis as a Drug Target

Supuran

Capasso

2017

Pathogens

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Periodontitis originates from a microbial synergy causing the development of a mouth microbial imbalance (dysbiosis), consisting of a microbial community composed of anaerobic bacteria. Most studies concerning the treatment of periodontitis have primarily take into account the Gram-negative bacterium Porphyromonas gingivalis, because it is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. Here, we focus our attention on the study of the carbonic anhydrases (CAs, EC 4.2.1.1) encoded in the genome of this pathogen as a possible drug target. Carbonic anhydrases are a superfamily of metalloenzymes, which catalyze the simple but physiologically crucial reaction of carbon dioxide hydration to bicarbonate and protons. Bacterial CAs have attracted significant attention for affecting the survival, invasion, and pathogenicity of many microorganisms. The P. gingivalis genome encodes for two CAs belonging to β-CA (PgiCAβ) and γ-CA (PgiCAγ) families. These two enzymes were cloned, heterologously expressed in Escherichia coli, and purified to homogeneity. Moreover, they were subject to extensive inhibition studies using the classical CA inhibitors (sulfonamides and anions) with the aim of identifying selective inhibitors of PgiCAβ and PgiCAγ to be used as pharmacological tools for P. gingivalis eradication.

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“…In this context, we investigated a rather large number of sulfonamides and their bioisosteres for their interaction with MreCA. A library of 40 compounds, 39 primary sulfonamides and one sulfamate, were used as CAIs [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. Figure 3 indicates the molecular structures of these compounds.…”

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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Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

Cited by 55 publications

References 82 publications

An Overview of the Bacterial Carbonic Anhydrases

An Overview of the Bacterial Carbonic Anhydrases

Carbonic Anhydrase from Porphyromonas Gingivalis as a Drug Target

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

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