Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria

Abstract

A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-β), Burkholderia pseudomallei (BpsCA-β and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-β) and the Salmonella enterica serovar Typhimurium (StCA2-β). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.

Sweet Selenium: Synthesis and Properties of Selenium-Containing Sugars and Derivatives

“…Organoselenium compounds are gaining interest in the medicinal chemistry community due to their promising biological activities for a wide range of clinical applications [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Starting from Ebselen, the first compound showing the ability to function as glutathione peroxidase (GPx) mimetic [ 8 ], several Se-bearing molecules were reported as anticancer [ 9 , 10 , 11 , 12 ], anti-inflammatory [ 13 , 14 ], antidepressant [ 15 , 16 ], and antibacterial [ 17 , 18 , 19 ], among others.…”

Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation

“…For the acesulfame derivatives (50-60), closed saccharins (1)(2)(3)(4)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) as well as the opened ones containing the ester functional group (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), were employed the two eluents water (solvent A) and acetonitrile (solvent B) mixed in the constant ratio of 50:50 (v:v). For the opened saccharins containing the carboxylic acid group (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(47)(48)(49) the two solvents were added with 0.1% of trifluoroacetic acid (TFA) mai...…”

“…All the compounds have been characterised by melting point, TLC parameters, 1 H and 13 C NMR. Their purity was evaluated through HPLC analysis, employing two different methods: the first used for acesulfame derivatives (50-60), closed saccharins (1-4, 29-46) as well as opened saccharins containing methyl ester group (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16); the second one used for opened saccharin derivatives with carboxylic acid group (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(47)(48)(49). In particular, the compounds were analysed using isocratic elution with a binary mobile phase composed by water and acetonitrile (added of 0.1% with trifluoroacetic acid for the acidic derivatives) and were !96% HPLC pure (See Supporting information).…”

“…In this regard, three different "sub-series" were evaluated. The first (5-16) is based on the opened saccharin core containing the methyl ester group in spite of the carboxylic acid one that is present in the second subgroup (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). All these derivatives have on the carbon atom neighbouring to the one bearing the ester/carboxylic acid functional groups, a secondary sulphonamide whose the nitrogen atom binds to a (un)substituted phenyl rings.…”

“…Unceasing efforts have been done and a lot of studies are ongoing aimed at discovering novel chemical libraries able to effectively inhibit hCA IX and XII [19][20][21][22] . Albeit classical CAs inhibitors take advantage of the presence of primary sulphonamide group 10,[23][24][25][26] , in the last years a large number of compounds devoid of this chemical functionality have been discovered and evaluated as effective hCAs inhibitors [27][28][29][30] . Among the scaffolds frequently used for the development of "non classical" inhibitors of human carbonic anhydrases, saccharin and acesulfame have a great importance.…”