Mersalyl acid

Folic Acid 460.6 Fluocortolone Pivalate 483.9 Mersalyl Acid... 

Fig. 10.5. Notable examples of Rcelp inhibitors. Abbreviations shown refer to At,-tosyl-l-phenylalanine chloromethyl ketone (TPCK), p-hydroxymercnribenzoic acid (pHMB), p-hydroxymercuriphenylsulfonic acid (pHMS), mersalyl acid (MSA), (acyloxy)methyl ketone (AOMK), and National Service Center (NSC).

Nine organomercury compounds (e.g., methyl-, methoxyethyl-, phenyl-, tolyl-and benzoyl-mercury nitromersol and mersalylic acid) were baseline resolved on a C g column (A = 230nm) using a 25min 30/70 -y 50/50 methanol/water (50 mM ammonium acetate buffer at pH 5.0 with 0.1 mM 2-mercaptoethanol) gradient [147]. Note that the mercaptoethanol has a strong stench and so the system should be located in a well-ventilated area. Detection limits fi om 7 to 95 pg/L were reported (analyte dependent). 

Table 7.3. Effects of various inhibitors on [a32P]ADP uptake into E. coli cells expressing several adenine nucleotide carriers. E. coli cells were preincubated for 10 min with lysozyme (2.5 mg/ml) to allow penetration of the reagents across the outer membrane. The inhibitors used were bongkrekic acid (BKA, 50 pM), carboxyatractyloside (CAT, 1 mM), N-elhylmaleimide (NEM, 1 mM), pyridoxal 5 -phosphate (PLP, 2 mM), and mersalyl (100 pM). [a32P]ADP uptake by AAC2(A.t.), AACKN.sp.), HMP31(Tg.), and ANTI (H.h.) was measured at a substrate concentration of 10, 100, 50, and 200 pM, respectively (Voncken et al. 2002 Tjaden et al. 2004 Leroch et al. 2005 Leroch 2006)...

Lovenberg, Buchanan, and Rabinowitz (65) tested the response of ferredoxin to mercury compounds. Two mercurial reagents used, p-mer-curibenzoate (PCMB) and o-((3-hydroxymercuri-2-methoxypropyl)car-bamyl)phenoxyacetate (sodium mersalyl) reacted rapidly with ferredoxin and caused a bleaching of the visible spectrum and a concomitant loss of biological activity. C. pasteurianum ferredoxin was titrated with PCMB as described by Boyer (24) and the results showed that 20 moles of PCMB reacted with 1 mole of ferredoxin. In another determination, 2 moles of PCMB reacted with 1 mole of sodium sulfide. Since ferredoxin contained 7 moles of inorganic sulfide and 8 moles of half-cystine residues, 22 (7 x 2 = 14 14 + 8 = 22) moles of PCMB would be expected to react with 1 mole of ferredoxin. These data, summarized in Table 8, are consistent with the existence of two types of sulfur in ferredoxin. This conclusion was supported by the presence of half-cystine residues in ferredoxin after inorganic sulfide had been removed by acid hydrolysis, as well as results of sulfur analyses, which showed an amount of sulfur greater than could be attributed to half-cystine residues. 

In mitochondrial research the phosphate-transporting protein from rat liver mitochondria has been labeled with ° Hg-mersalyl At For protein labeling with astatine (alpha emitter) the following procedures may be u reaction of the protein with p-astatobenzoic acid < ndensation reaction with peptide bond and protein acetylation While labeling by the above procedures seems to be sufficiently stable a remarkable instability of the At-label was obserwd when astatinated protein was prepared electrophoretically 202) jjjg results of these authors indicate that the tyrosine-astatine bond is unstable. The conclusion of Vau an et al. that astatinated proteins lore as much as 50% of their biological activity and, in addition, are extremely toxic, is very serious. 

The Polish proprietary medicine Dehydrit is described in Gehe s Codex (3rd supplement, 1950) as the sodium salt of o-[(3-hydroxymercuri-2-methoxypropyl) carbamyl]phenoxyacetic acid dissolved in aqueous itheophylline solution. This preparation is known in the U. S. Pharmacopeia as Mersalyl and theophylline injection, and in the U. S. Dispensatory (page 700, 24th edition) the pharmacist is informed of the United States equivalent in the form of Salyrgan-Theophylline Ampuls (Winthrop). 

D. Diuretics Acetazolamide, bumetanide, chlortalidone, etacrynic acid, furosemide, hydrochlorothiazide, mannitol, mersalyl, spironolone, triamterene and related substances... 

Ethacrynic acid (Table 10-11) is a powerful loop diuretic whose molecular mechanism of action is not fully clear. However, it has marked pharmacodynamic similarities to the mercurial diuretics such as merbaphen (see above) and mersalyl, both of which are also phenoxyacetic acid derivatives, as well as in vitro and in vivo comparability in its reaction with SH groups It competes with them for the same receptors. It is not surprising that an analogy, if not identity, of mechanism of action at the cellular level has been proposed. Equation 10.5, which illustrates a Michael-type addition, might represent a possible enzyme inactivation. 

Mersalyl may be determined directly on 5 ml either by the acid reduction method of Pierce or by hydrolysis and sulphide precipitation, as follows ... 

Other compounds tested for their ability to inhibit or activate sialidase include iodoacetamide (10 m). AT-ethylmaleimide (10 m) and Mersalyl (10 m). On partially purified sialidase from pig kidney, these had no effect (Tuppy and Palese, 1968) a-chymotrypsin with sialidase from bovine brain caused an increase in activity (Gielen and Harprecht, 1969) EDTA, p-hydroxymercuribenzoate (formerly was believed to be p-chloromercuribenzoate), tested on sialidase in rat liver and kidney, had no effect (Mahadevan et al., 1967) the bacterial inhibitors 2-deoxy-2,3-dehydroneuraminic acid and p-nitrophenyloxamic acid tested on purified sialidase from rat heart muscle had no effect (Tallman and Brady, 1973) while l-(4-methoxyphenoxymethyl)-3,4-dehydroisoquino-line and p-hydroxymercuribenzoate were inhibitory with ganglioside Goia substrate. The effect of specific inhibitors on purified sialidase may give useful information about the active site, an unknown entity at this time. 

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