Isatin analogs as novel inhibitors of Candida spp. β-carbonic anhydrase enzymes

Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities

“…The synthesis of cyclic thioureas related to the title compounds has been reported in the literature [69][70][71][72][73] . By a similar approach, the reaction of substituted p-tolualdehyde, p-anisaldehyde, o-tolualdehyde, salicylaldehyde and benzaldehyde with methylene active compounds such as b-diketones and thiourea in the presence of TFAA led to the desired cyclic thioureas (1)(2)(3)(4)(5)(6)(7)(8) …”

“…Cyclic thioureas 1, 4 and 8, which possesses a phenolic moiety in its scaffolds demonstrated effective antioxidant activities. The enzymes inhibition and antioxidant activities data of cyclic thioureas (1)(2)(3)(4)(5)(6)(7)(8) reported here are shown in Tables 1-3, and the following comments can be drawn from these data: (1) The cytosolic isoenzymes CA I, and II are examined in this study. Cytosolic hCA I isoenzyme is ubiquitously expressed in body, and available in high concentrations in blood and gastrointestinal tract 106 .…”

“…Metal chelating ability of cyclic thioureas (1-8) was predicted according to previous studies [96][97][98] . Fe 2+ -binding capacity of cyclic thioureas (1)(2)(3)(4)(5)(6)(7)(8) was spectrophotometrically recorded at 562 nm. In brief, to a mixture of FeCl 2 (0.1 mL, 0.6 mM) cyclic thioureas (1-8) were added at three different concentrations (10-20 mg/mL) in methanol (0.4 mL).…”

“…Indeed, bicarbonate is a substrate for several carboxylation enzymes involved in biosynthetic pathways such as biosynthesis of urea, glucose, fatty acids and possibly nucleotides [7][8][9][10] . The reaction not only provides a means to control the physiological pH values, but also supplies HCO 3 À ions for various physiological processes or metabolic, biosynthetic pathways, as those mentioned above [11][12][13][14] . So far, six unrelated genetic CA families have been discovered, namely, the a-, b-, g-, d-, z-and Z-CAs.…”

“…1,2 The reversible hydration of carbon dioxide (CO 2 ) to form bicarbonate (HCO 3 À ) and protons (H + ) is a simple but very important chemical reaction that can be performed by various classes of carbonic anhydrases (CAs, EC 4.2.1.1). [3][4][5][6] The interconversion of CO 2 and HCO 3 À is spontaneously balanced to maintain the equilibrium between dissolved inorganic CO 2 , the highly unstable carbonic acid (H 2 CO 3 ) and carbonate (CO 3 2À ) of which HCO 3 À is physiologically the most important species (due to the physiological pH values). Indeed, bicarbonate is a substrate for several carboxylation enzymes involved in biosynthetic pathways such as biosynthesis of urea, glucose, fatty acids and possibly nucleotides [7][8][9][10] .…”