- Development of potent carbonic anhydrase inhibitors incorporating both sulfonamide and sulfamide groups
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A series of compounds incorporating both sulfonamide and sulfamide as zinc-binding groups (ZBGs) are reported as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Crystallographic studies on the complex of hCA II with the lead compound of this series, namely, 4-sulfamido- benzenesulfonamide, revealed the binding of two molecules in the enzyme active site cavity, the first one canonically coordinated to the zinc ion by means of the sulfonamide group and the second one located at the entrance of the cavity. This observation led to the design of elongated molecules incorporating these two ZBGs, separated by a linker of proper length, to allow the simultaneous binding to these different sites. The long inhibitors indeed showed around 10 times better enzyme inhibitory properties as compared to the shorter molecules against four physiologically relevant human (h) isoforms, hCA I, II, IX, and XII.
- D'Ambrosio, Katia,Smaine, Fatma-Zhora,Carta, Fabrizio,De Simone, Giuseppina,Winum, Jean-Yves,Supuran, Claudiu T.
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experimental part
p. 6776 - 6783
(2012/09/21)
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- Hapten synthesis and development of polyclonal antibody-based multi-sulfonamide immunoassays
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This paper reports the synthesis of five sulfonamide derivatives, the production of broad-specificity polyclonal antibodies for immunoassay of sulfonamides, and the analysis of milk samples by developed assay. The three-step synthesis procedure reported in most of the literature was adopted and modified in this study. In the procedure, the purification of the intermediate was avoided and the time of synthesis was shortened from >20 to 6-9 h with improved yields. This method is generally applicable to the synthesis of haptens containing the common structure of sulfonamides. Three haptens were coupled to keyhole limpet hemocyanin, and polyclonal antibodies were obtained from rabbits immunized with these conjugates. Using the antibodies obtained, from one of these was developed an enzyme-linked immunosorbent assay (ELISA) based on the competition between free sulfonamides and the hapten-horseradish peroxidase (HRP) conjugates. The hapten-HRP conjugate giving the best competitive results and 11 structurally different sulfonamides showed 50% inhibition at concentrations of -1. After removal of the protein with acetone, milk samples were analyzed by ELISA directly; a matrix effect could be avoided when a 1:20 dilution with phosphate-buffered saline was used, and 104-131% recoveries of spiked samples were obtained. The developed immunoassay is suitable to determine sulfisozole, sulfathiazole, sulfameter, sulfamethoxypyridazine, sulfapyridine, and sulfamethizole below the maximum residue limit in milk (100 ng mL-1 of total sulfonamides) rapidly and reliably.
- Zhang, Hongyan,Duan, Zhenjuan,Wang, Lei,Zhang, Yan,Wang, Shuo
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p. 4499 - 4505
(2007/10/03)
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- Synthesis of sulfanilamido-naphthoquinones as potential antituberculous agents
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p-Aminobenzoic acid, the acid hydrazides of benzoic acid, salicylic acid and isonicotinic acid, and 4,4'-diaminodiphenyl sulfone were condensed with p-aminobenzenesulfonyl chloride to give the corresponding N1-substituted sulfanilamides. These molecules were then treated with 1,4-naphthoquinone to yield 2-substituted-1,4-naphthoquinones. The partition coefficient for the substituted quinones showed, in some cases, high diffusion rates to the organic phase, benzene, from physiological Tyrode's solution. These compounds are effective in low concentration in dioxane against the human sensitive strain of Mycobacterium tuberculosis H37 Rv. Sulfanilamides obtained from p-aminosalicylic acid and thiosemicarbazide failed to react with 1,4-naphthoquinone. These sulfanilamides also showed high activity against the same Mycobacterium.
- Osman,Abdalla,Alaib
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