Exploring structural properties of potent human carbonic anhydrase inhibitors bearing a 4-(cycloalkylamino-1-carbonyl)benzenesulfonamide moiety

Seeking new approach for therapeutic treatment of cholera disease via inhibition of bacterial carbonic anhydrases: experimental and theoretical studies for sixteen benzenesulfonamide derivatives

“…This series of compounds has been rationally designed by using the cycloalkylamine nucleus as the core for binding contact in the middle area of catalytic site ( Figure 1). The visual inspection of their binding mode in co-crystal adducts with hCA II and hCA VII confirmed that the sulfonamide portion is crucial for CA recognition process 23 . By considering the high inhibitory effects of this series of potent sulfonamide compounds, we decided to further study their CA inhibitory profile thus exploiting their capability to act as potential anti-infective agents.…”

“…As displayed in Scheme 1, the studied 4-(cycloalkyl)-1-carbonylbenzenesulfonamides 5a-e, 6a, 7a-f, 8a-d have been resynthesised following a synthetic procedure previously reported by us 23 ; experimental details can be found in "Materials and Methods" section as well as in Supporting Material.…”

“…The obtained results are summarised in Table 1 and compared with the wellknown inhibitor AAZ (1). Moreover, the K i values measured against bacterial CAs were compared with an affinity towards selected human CA isoforms hCA I and hCA II 23 .…”

“…Recently, we have studied a new small library of CAIs containing azepine/piperidine/piperazine nucleus linked to benzenesulfonamide fragment and disclosed several compounds that demonstrated inhibitory effects in low nanomolar range toward hCAs 23 . This series of compounds has been rationally designed by using the cycloalkylamine nucleus as the core for binding contact in the middle area of catalytic site ( Figure 1).…”

The crystal structures of 2-(4-benzhydrylpiperazin-1-yl)-N-(4-sulfamoylphenyl)acetamide in complex with human carbonic anhydrase II and VII provide insights into selective CA inhibitor development

“…[13][14][15] Three different classes of CA inhibitors (CAIs) have been characterized so far: (i) molecules that bind to the catalytic zinc ion, such as primary sulfonamides and their isosteres (sulfamates and sulfamides), 16,17 dithiocarbamates, 18 and xanthates; 19 (ii) molecules which anchor to the zinc-coordinated water molecule/hydroxide ion, as observed for phenols 20,21 and polyamines; 22 (iii) compounds occluding the active site entrance, as reported for coumarins 23,24 and lacosamide. 25 Several inhibitors belonging to these classes have been designed and tested against hCA VII, [26][27][28][29] however, although showing good inhibition efficiency, they are generally poorly selective; for this reason, new molecules are continuously synthesized and tested to identify more selective hCA VII inhibitors.…”