Potent inhibitor of isozymes of human monoamine oxidaze, namely hCA I, hCA II, bCA IV (membrane-bound isozyme) and mCA V (mitochondrial), with IC50 = 3300 nM, 37 nM, 176 nM and 17 nM, respectively. (Ref. 1).
Potent inhibitor of isozymes of human monoamine oxidaze, namely hCA I, hCA II, hCA IX and hCA XII, with IC50 = 3300 nM, 37 nM, 73 nM and 21 nM, respectively. (Ref. 2).
OTAVAchemicals Catalogue Number: 0127441873
CAS Registry Number: N/A
Ref. 1: Vullo et al. Carbonic Anhydrase Inhibitors. Inhibition of Mitochondrial Isozyme V with Aromatic and Heterocyclic Sulfonamides. J. Med. Chem. (2004), 47, 1272-1279.
Abstract: The first inhibition study of the mitochondrial isozyme carbonic anhydrase (CA) V (of murine origin) with a series of aromatic and heterocyclic sulfonamides is reported. Inhibition data of the cytosolic isozymes CA I and CA II and the membrane-bound isozyme CA IV with these inhibitors are also provided for comparison. Several low nanomolar CA V inhibitors were detected (Ki values in the range of 4-15 nM), most of them belonging to the acylated sulfanilamide, ureido-benzenesulfonamide, 1,3,4-thiadiazole-2-sulfonamide, and aminobenzolamide type of compounds. The clinically used inhibitors acetazolamide, methazolamide, ethoxzolamide, dorzolamide, brinzolamide, and topiramate on the other hand were less effective CA V inhibitors, showing inhibition constants in the range of 47-63 nM. Some of the investigated sulfonamides, such as the ureido-benzenesulfonamides and the acylated sulfanilamides showed higher affinity for CA V than for the other isozymes, CA II included, which is a remarkable result, since most compounds investigated up to now inhibited the cytosolic isozyme CA II better. These results prompt us to hypothesize that the selective inhibition of CA V, or the dual inhibition of CA II and CA V, may lead to the development of novel pharmacological applications for such sulfonamides, for example in the treatment or prevention of obesity, by inhibiting CA-mediated lipogenetic processes.
Ref. 2: Ö. Özensoy et al. Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with a library of aromatic and heteroaromatic sulfonamides. Bioorg. Med. Chem. Lett. 15 (2005) 4862–4866.
Abstract: The inhibition of the two transmembrane, tumor-associated isozymes of carbonic anhydrase (CA, EC 22.214.171.124) of human origin, hCA IX and XII, with a library of aromatic and heteroaromatic sulfonamides has been investigated. Most of them were sulfanilamide, homosulfanilamide, and 4-aminoethyl-benzenesulfonamide derivatives, to which tails that should induce diverse physico-chemical properties have been attached at the amino moiety, whereas several of these compounds were derived from metanilamide, benzene-1,3-disulfonamide or the 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides. The tails were of the alkyl/aryl-carbox-amido/sulfonamido-, ureido or thioureido type. Against hCA IX the investigated compounds showed inhibition constants in the range of 3–294 nM, whereas against hCA XII in the range of 1.9–348 nM, respectively. The best hCA IX inhibitors were ureas/thioureas incorporating 4-aminoethyl-benzenesulfonamide and metanilamide moieties. The best hCA XII inhibitors were 1,3,4-thiadiazole/thiadiazoline-2-sulfonamides incorporating 5-acylamido or 5-arylsulfonylamido moieties. These compounds also inhibited appreciably the cytosolic isozymes hCA I and II, but some selectivity for the transmembrane, tumor-associated isozymes was observed for some of them, which is an encouraging result for the design of novel therapies targeting hypoxic tumors, in which these carbonic anhydrases are highly overexpressed.