Abstract
Carbonic Anhydrases (CAs) are ubiquitous metalloenzymes involved in several disease conditions. There are 15 human CA (hCA) isoforms and their high homology represents a challenge for the discovery of potential drugs devoid of off-target side effects. For this reason, many synthetic and pharmacologic research efforts are underway to achieve the full pharmacological potential of CA modulators of activity. We report here a novel series of sulfanilamide derivatives containing heterocyclic carboxamide moieties which were evaluated as CA inhibitors against the physiological relevant isoforms hCA I, II, IX, and XII. Some of them showed selectivity toward isoform hCA II and hCA XII. Molecular docking was performed for some of these compounds on isoforms hCA II and XII to understand the possible interaction with the active site amino acid residues, which rationalized the reported inhibitory activity.
Highlights
Carbonic anhydrases (CAs) are a ubiquitous metalloenzyme family present in both eukaryote and prokaryote organisms [1]
N-(4-sulfamoylphenyl)Taking into account all of the mentioned above, here we report the synthesis of N-(44H-furano[3,2-b]pyrrole-5-carboxamide derivatives incorporating into one scaffold carsulfamoylphenyl)-4H-thieno[3,2-b]pyrrole-5-carboxamide and N-(4-sulfamoylphenyl)boximide and sulfonamide moieties
The structure–activity relationship studies revealed that the presence of 3-phenyl5,6-dihydro-1,4-dioxine-2-carboxamide (14a) as a substituent at the para- position of benzenesulfonamide is very beneficial for inhibitory activity against human CA (hCA) I
Summary
Carbonic anhydrases (CAs) are a ubiquitous metalloenzyme family present in both eukaryote and prokaryote organisms [1]. To date, were discovered eight evolutionarily unrelated gene classes encoded as α-, β-, γ-, δ-, ζ-, η-, θ-, ι-CAs [2,3,4,5,6,7,8] All these enzymes promoting the hydration of carbon dioxide (CO2 ) to bicarbonate (HCO3 − ) and protons (H+ ). Abnormal levels or activities of these enzymes have been often associated with different human diseases, some of which have been clinically exploited and validated as therapeutic targets for the treatment or prevention of various pathologies such. 6-oxo[1,3]thiazolo[3,2in silico techniques, aimed to propose a reliable binding disposition for this class of CAIs. b][1,2,4]triazole derivatives were synthesized.
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