N -Sulfamoylphenyl- and N -sulfamoylphenyl- N -thiazolyl-β-alanines and their derivatives as inhibitors of human carbonic anhydrases

“…A quite different approach was used by the Matulis group [ 67 , 68 ] to derive p -amino benzenesulfonamide. By reacting the p -amino group with acrylic acid, Rutkauskas et al obtained a series of compounds where a β-alanyl moiety is directly linked to the aromatic scaffold (general formula 37 and 38 , Figure 17 ).…”

Section: Amino Acids As Linkersmentioning

confidence: 99%

“…Only in a few instances the activity of this first series of compounds (K d values determined by a fluorescent thermal shift assay on CA I, II, VI, VII, XII and XIII) was below 1 μM. The functionalization of the alanyl nitrogen and substitution on the benzenesulfonamide ring were also investigated, adding other possible points of variation [ 68 ]. As one can imagine, this large number of different products showed a wide range of activities, with K d values on CA I, II, XII and XIII from nanomolar to micromolar.…”

Section: Amino Acids As Linkersmentioning

confidence: 99%

Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors

et al. 2018

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Carbonic anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life, classified into seven genetically different families (α–θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3−) and protons (H+). Fifteen isoforms of human CA (hCA I–XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) have been used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

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“…Over the years, a lot of biologically important α‐amino acids with various substituents in their molecules have been synthesized from many different carbonyl compounds, and it was found that they possess analgesic and anti‐inflammatory, [16,17] anticancer, [18] antiprotozoal, [19] antibacterial [20] activity, inhibit monoamine oxidase (MAO−B) activity, [21] demonstrate potent effect against ischemia‐reperfusion induced cardiac infarct size [22] . Using benzenesulfonamide as a scaffold, the novel derivatives substituted at 4‐position with fragments of natural amino acids were prepared, which possessed CA inhibition activity [23–25] . Several dibrominated and dichlorinated benzenesulfonamides bearing β‐alanine fragments [24] displayed high affinity and selectivity for CA VB isozyme over cytosolic CA I and CA II and mitochondrial CA VA isozymes (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Using benzenesulfonamide as a scaffold, the novel derivatives substituted at 4‐position with fragments of natural amino acids were prepared, which possessed CA inhibition activity [23–25] . Several dibrominated and dichlorinated benzenesulfonamides bearing β‐alanine fragments [24] displayed high affinity and selectivity for CA VB isozyme over cytosolic CA I and CA II and mitochondrial CA VA isozymes (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Hydrazone‐Bearing Benzenesulfonamides as Carbonic Anhydrase VB Inhibitors

et al. 2021

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The α‐amino acid derivatives are constituents of many bioactive compounds and display a wide variety of biological activities. We have synthesized a series of new benzenesulfonamide derivatives bearing α‐amino acid moiety at para‐position and evaluated their binding affinity to human carbonic anhydrase isozymes by fluorescent thermal shift assay. The dichloro‐ and monobromo‐substitutions on the benzenesulfonamide ring have been introduced to determine the halogenation effect on the binding affinity. Chloro substituents at 3,5‐positions of benzenesulfonamide derivatives increased the affinity for all carbonic anhydrases as compared to non‐chlorinated compounds. The hydrazone‐bearing 3,5‐dichlorobenzenesulfonamides 9 a, 9 d, and 12 exhibited a low nanomolar affinity for CA VB (Kd in the range of 6.6–8.1 nM), an isozyme implicated in diseases of the central nervous system and obesity.

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N -Sulfamoylphenyl- and N -sulfamoylphenyl- N -thiazolyl-β-alanines and their derivatives as inhibitors of human carbonic anhydrases

Cited by 15 publications

References 37 publications

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors

Design and Synthesis of Hydrazone‐Bearing Benzenesulfonamides as Carbonic Anhydrase VB Inhibitors

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