Chromene-Containing Aromatic Sulfonamides with Carbonic Anhydrase Inhibitory Properties

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the essential reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of chromene-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I, hCA II and the transmembrane hCA IX and XII. Several of the investigated derivatives showed interesting inhibition activity towards the tumor associate isoforms hCA IX and hCA XII. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

“…The aim of this study is to support and extend our previous studies [ 51 , 52 , 53 ] on hCA as a target against diverse pathological conditions. Thus, herein we report the synthesis of two different groups of compounds, one of which is pyrazolo[4,3-c]pyridine sulfonamides ( 1a – f ) and the other sulfonamide derivatives of different hetrocyclic moieties ( 1g–1k ), and the evaluation of their inhibitory activities towards four human CAs (I, II, IX, and XII) as well as 3β and 3γ CAs from different bacterial strains.…”

“…Protein Data Bank was also used in order to obtain the crystal structures of hCA I (PDB code: 3W6H) and hCA II (PDB code: 3HS4) cytosolic isoforms, hCA IX (PDB code: 3IAI) and hCA XII (PDB code: 1JD0) transmembrane tumor-associated isoforms, and E. coli β-carbonic anhydrase (PDB code: 1IP6) and γ-carbonic anhydrase (PDB code: 1QRL) [ 71 ]. All the procedures were carried out as in our previous work [ 53 ].…”

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety

“…Investigated structures that have effective binding capabilities in the CA site mainly contain the sulfonamide pharmacophore moiety . Our aim was to synthesize hybrid molecules characterized by pyrrol-2-one as a core and two active binding groups on its sides (Figure ).…”

“…Aiming to produce new derivatives in light of all of the above, our current work was a continuation of our earlier investigation into N -heterocycle systems − and as part of our interest in the field of physiologically active chemicals, − with a focus on carbonic anhydrase inhibitors. ,,,− The synthesis, structure, and evaluation of several novel dihydro-pyrrol-2-one derivatives as inhibitors of tumor-associated human CA are thus reported here.…”

Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors

“…Protein Data Bank was also used in order to obtain the he crystal structures of hCA I (PDB code 3W6H) and hCA II (PDB code 3HS4) cytosolic isoforms as well as hCA IX (PDB code 3IAI) and hCA XII (PDB code 1JD0) transmembrane tumor-associated isoforms [48]. All of the procedure was carried out as described in our previous work [49].…”