3523-96-4Relevant articles and documents
Development of sulfonamide AKT PH domain inhibitors
Ahad, Ali Md.,Zuohe, Song,Du-Cuny, Lei,Moses, Sylvestor A.,Zhou, Li Li,Zhang, Shuxing,Powis, Garth,Meuillet, Emmanuelle J.,Mash, Eugene A.
experimental part, p. 2046 - 2054 (2011/05/05)
Disruption of the phosphatidylinositol 3-kinase/AKT signaling pathway can lead to apoptosis in cancer cells. Previously we identified a lead sulfonamide that selectively bound to the pleckstrin homology (PH) domain of AKT and induced apoptosis when present at low micromolar concentrations. To examine the effects of structural modification, a set of sulfonamides related to the lead compound was designed, synthesized, and tested for binding to the expressed PH domain of AKT using a surface plasmon resonance-based competitive binding assay. Cellular activity was determined by means of an assay for pAKT production and a cell killing assay using BxPC-3 cells. The most active compounds in the set are lipophilic and possess an aliphatic chain of the proper length. Results were interpreted with the aid of computational modeling. This paper represents the first structure-activity relationship (SAR) study of a large family of AKT PH domain inhibitors. Information obtained will be used in the design of the next generation of inhibitors of AKT PH domain function.
Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives
Ilies, Marc A.,Vullo, Daniela,Pastorek, Jaromir,Scozzafava, Andrea,Ilies, Monica,Caproiu, Miron T.,Pastorekova, Silvia,Supuran, Claudiu T.
, p. 2187 - 2196 (2007/10/03)
Two series of halogenated sulfonamides have been prepared. The first consists of mono/ dihalogenated sulfanilamides, whereas the second one consists of the mono/dihalogenated aminobenzolamides, incorporating equal or different halogens (F, Cl, Br, and I). These sulfonamides have been synthesized from the corresponding anilines by acetylation (protection of the amino group), chlorosulfonylation, followed either by amidation, or reaction with 5-amino1,3,4-thiadiazole-2-sulfonamide (and eventually deacetylation). All these compounds, together with the six clinically used sulfonamide inhibitors (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, and brinzolamide) were investigated as inhibitors of the transmembrane, tumor-associated isozyme carbonic anhydrase (CA) IX. Inhibition data against the classical, physiologically relevant isozymes I, II, and IV were also obtained. CA IX shows an inhibition profile which is generally completely different from those of isozymes I, II, and IV, with potent inhibitors (inhibition constants in the range of 12-40 nM) among both simple aromatic (such as 3-fluoro-5-chloro-4-aminobenzenesulfonamide) as well as heterocyclic compounds (such as acetazolamide, methazolamide, 5-amino-1,3,4-thiadiazole-2-sulfonamide, aminobenzolamide, and dihalogenated aminobenzolamides). This first detailed CA IX inhibition study revealed many interesting leads, suggesting the possibility to design even more potent and eventually CA IX-selective inhibitors, with putative applications as antitumor agents.
Renal and cerebrospinal fluid formation pharmacology of a high molecular weight carbonic anhydrase inhibitor
Maren, Thomas H.,Conroy, Curtis W.,Wynns, George C.,Godman, David R.
, p. 98 - 104 (2007/10/03)
To achieve selective inhibition of cytosolic and membrane-bound carbonic anhydrase (CA II and CA IV, respectively), we synthesized a polymer of molecular weight 3500 from polyoxyethylene bis acetic acid and aminobenzolamide. The new compound, designated F
