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

Morteza Abdoli,Claudiu Supuran,Murat Bozdag,Andrea Angeli

doi:10.3390/metabo8020037

Morteza Abdoli, Claudiu Supuran + Show 2 more

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https://doi.org/10.3390/metabo8020037

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Journal: Metabolites	Publication Date: Jun 1, 2018
Citations: 19	License type: CC BY 4.0

Affiliation: Lorestan University, University of Florence

Abstract

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.

Highlights

Hydroxybenzotriazole has been used for synthesis, as reported previously [1,2] (Scheme 1)
We report a series of benzamides incorporating 4-sulfamoyl moieties, which were obtained by reacting 4-sulfamoyl benzoic acid with primary and secondary amines and amino acids
These sulfonamides were investigated as inhibitors of several enzymes, including the human (h) isoforms hCA II, VII, and IX, involved in severe pathologies, such as glaucoma, epilepsy, neuropathic pain and cancer; and β- and γ-class CAs from pathogenic bacteria and fungi. hCA II, VII, and IX were inhibited in the low nanomolar or subnanomolar ranges by all investigated sulfonamides, whereas hCA I was slightly less sensitive to inhibition (KI s of 5.3–334 nM)

Summary

Introduction

Benzamides incorporating 3- or 4-sulfamoyl moieties, such as derivatives A and B (Figure 1)Benzamides incorporating 3- or 4-sulfamoyl moieties, such as derivatives A and B (Figure 1) were were investigated [1,2] as inhibitors of the zinc metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1)investigated [1,2] as inhibitors of the zinc metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1) [3,4,5,6,7,8,9,10,11,12][3,4,5,6,7,8,9,10,11,12] in this study, in the search of agents with intraocular pressure lowering effects [1,2]. Benzamides incorporating 3- or 4-sulfamoyl moieties, such as derivatives A and B (Figure 1) were were investigated [1,2] as inhibitors of the zinc metallo-enzyme carbonic anhydrase (CA, EC 4.2.1.1). The incorporation incorporation of a wide range of amino acid (AA) or dipeptide AA moieties in molecules A and B led of a wide range of amino acid (AA) or dipeptide AA moieties in molecules A and B led to enhanced to enhanced water solubility for topical administration within the eye. These compounds showed water solubility for topical administration within the eye.

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Discussion

Conclusion