Sulphonamide drugs

Figure 8.6 Competitive inhibition. Sulphonamide drugs compete with p-amino-benzoic acid, which is an essential growth factor for many bacteria.

Hartig C, Storm T, Jekel M (1999). Detection and identification of sulphonamide drugs in municipal wastewater by liquid chromatography coupled with electrospray ionisation tandem mass spectrometry. J Chromatography A 854 163-173 Hayes HM, Tarone RE, Cantor KP (1995) On the association between canine mahgnant lymphoma and opportunity for exposure to 2,4-dichlorophenoxyacetic acid. Environ Res 70 119-125... 

Sulphonamide antimicrobial agents (Figure 8.22) such as sulphamethoxazole [21] are oxidized to protein-reactive cytotoxic metabolites in the liver and also other tissues. These include hydroxylamines and further products such as nitroso-deriva-tives. Sulphonamide drugs are linked with agranulocytosis, aplastic anaemia and... 

G Alfredsson, A Ohlsson. Stability of sulphonamide drugs in meat during storage. Food Additiv Contain 15 302-306, 1998. 

C. Hartig, T. Storm, M. Jekel, Detection and identification of sulphonamide drugs in municipal waste water by LC-ESI-MS-MS, J. Chromatogr. A, 854 (1999) 163. 

More recently a study on sulphonamide drugs binding to the colchicines site of tubulin has been reported [38]. A series of diarylsulfonamides containing an indole scaffold was also found to have antimitotic properties, and to bind to the colchicine site of tubulin in a reversible manner. 

Most of the drugs have got the property to promote relatively stable oil in water emulsions. A study of a sulphonamide drug sulpha-pyridine reveals that it yields a stable emulsion. The emulsion behaviours have been interpreted by studying flocculation, coalescence, electro-kinetic potential, potential energies and stability factors. These studies were made as a function of nucleic acids, DNA and RNA (Deoxy-ribonucleic acid and Ribonucleic acid) which were chosen in accordance with their biological significance. 

The 13C NMR chemical shifts of eight sulphonamide drugs (sulphanilamide, sulpha-guanidine, sulphathiazole, sulphasuxidine, sulphadiazine, sulphamerazine, sulphameth-iazine and sulphapyridine) have been determined and assigned93. 

Kooij R, Van Vloten ThJ (1952) Epidermal sensitization due to sulphonamide drugs. Der-matologica 104 151-167... 

A competitive inhibitor resembles the substrate in its chemical structure and is able to combine with the enzyme to form an enzyme-inhibitor complex. In so doing it competes with the substrate for the active sites of the enzyme, and formation of the enzyme-substrate complex is inhibited. This type of inhibition may be reversed by the addition of excess substrate, which displaces the inhibitor, forming normal enzyme-substrate complexes. One of the best-known examples is provided by the sulphonamide drugs. The synthesis of folic acid from p-aminobenzoic acid (PABA) is a vital metabolic process in the bacteria controlled by these drugs. The similarity between PABA and sulphanUamide, released by the sulphonamides, is obvious ... 

McGrane, M. O Keeffe, M. Smyth, M.R. The analysis of sulphonamide drug residues in pork muscle using automated dialysis, Anal.Lett., 1999, 32, 481-495. [LOD 40 ng/g sulfadiazine sulfathiazole sulfapyridine sulfamerazine suRamethizole sulfamethazine sulfamethoxypyridazine sulfachlorpyridazine sulfisoxazole]... 

In general, nitrogen-containing heteroaromatic systems withdraw electrons from their substituents and this effect has been utilised in the control of the relative acidity of sulphonamide drugs. 

FIG. 3.7 Kinetics of the metabolism and excretion of sulphonamide drugs in the human body. (Nelson and O Reilly, i960.)... 

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