Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition

Design, synthesis and biological evaluation ofN-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors

“…However, the inhibition mechanism with secondary and tertiary sulfonamides is unknown, as no X-ray crystal structures of such derivatives bound to the CA are available to date. Thus, the sulfonamides reported here incorporate in their molecule the urea fragment found in SLC-0111 and the secondary sulfonamide moiety present in sulfa drugs and several recently investigated CAIs [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] .…”

“…In addition, a range of secondary and tertiary sulfonamides has been investigated as CAIs recently, some of them showing effective and selective inhibition of several important isoforms [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] . However, the inhibition mechanism with secondary and tertiary sulfonamides is unknown, as no X-ray crystal structures of such derivatives bound to the CA are available to date.…”

Synthesis of some tetrahydropyrimidine-5-carboxylates, determination of their metal chelating effects and inhibition profiles against acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase

“…a-CAs exist in 16 isoforms identified in various tissues and organs and differ in their cellular localization (cytosol, mitochondria or cell membrane), sensibility to inhibitors and catalytic activity [33][34][35] . Also, this CA family has molecular kinetic and different properties, oligomeric rearrangements and expression levels, as well as various abilities to respond to different inhibitory classes [36][37][38] . According to the known cellular localization, some of them are cytosolic (CA I, CA II, CA III, CA VII and CA XIII), some other CA isoenzymes are membrane bound (CA IV, CA IX, CA XII and CA XIV), two of CAs are mitochondrial (CA VA and CA VB) and one of CAs is salivary (CA VI) [39][40][41][42] .…”

Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid – sulfonamide conjugates

“…The metal ion may be in a tetrahedral or trigonal bipyramidal geometries, with the sulfonamides and their isosteres (sulfamides, sulfamates, etc. ), most anions, dithiocarbamates and their isosteres, carboxylates and hydroxamates binding in this way [1][2][3]5,13 ; (ii) the inhibitors that anchor to the zinc-coordinated water molecule/hydroxide ion, represented by the phenols, some carboxylates, the polyamines, 2-thioxocoumarins, and sulfocoumarins [1][2][3]13,14 ; (iii) the inhibitors which occlude the entrance to the active site cavity (coumarins and their isosteres), this binding site coinciding with that where CA activators bind [13][14][15][16][17][18][19][20] ; (iv) the compounds which bind out of the active site cavity (a carboxylic acid derivative was seen to inhibit CA in this manner) 21 , and (v) compounds for which the inhibition mechanism is not known, among which the secondary/tertiary sulfonamides as well as imatinib/nilotinib are the most investigated examples 13,[22][23][24][25][26] . The sulfonamides however remain the main class of CAIs with many clinically used drugs as antiglaucoma agents [27][28][29] , diuretics 30 , antiobesity drugs [31][32][33] , antiepilpetics 34 , and more recently agents for the management of hypoxic tumors [35][36][37][38] , neuropathic pain 39 and ischaemia …”