China
Africa
Explore chapters and articles related to this topic
Bioresponsive Hydrogels for Controlled Drug Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Tamgue Serges William, Dipali Talele, Deepa H. Patel
Among pH-responsive acidic polymers, commonly preferred are carboxylic, sulfonic, phosphoric, and boronic acids (BA), sulfonic, and phosphoric acids in hydrogels preparation. The obtained hydrogels swell well under basic conditions, when pH solution is superior to their pKa. The most widely used polymers containing sulfonic acid are poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS) and poly(4-styrenesulfonic acid) (PSSA) [36].
The Modification of Cysteine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
Cysteine is relatively sensitive to oxidation but there is little selectivity in these reactions. Mild oxidizing conditions can result in the formation of disulfide bonds with appropriately aligned cysteinyl residues. Formation of sulfenic acid is generally readily reversible unless stabilized by local conditions3 and more highly oxidized forms such as cysteine-sulfonic acid are more frequently observed. More rigorous conditions such as treatment with performic acid result in the formation of cysteic acid.
Disposition and Metabolism of Drugs of Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Morphine was first isolated by Sertürner in 1803. It constitutes approximately 8 to 12% by weight of opium depending on the geographical source. Its structural formula was proposed in 192531 and confirmed by total synthesis in 1952 and 1956.32a,b The levo isomer D(-)is responsible for the pharmacological activity, the d-isomer L(+) being inactive (Figure 1). The crystalline morphine monohydrate base m. 254 to 256°C has a pKa 8.02 to 8.05. Morphine sulfate is a fine crystalline odorless solid with a bitter taste. It is easily soluble in water and the pH of aqueous saturated solutions is 4.3 to 5.0. The olive oil/buffer (pH 7.4) partition coefficient of morphine is 0.4. A recent report33 describes an interaction of morphine and sodium bisulfite in aqueous solution to form a sulfonic acid derivative of dihydromorphinone. The usual analgesic dose of morphine by subcutaneous injection is 8 to 15 mg, 8 to 20 mg orally, and 2.5 to 15 mg by slow intravenous injection.
Small molecule glucagon receptor antagonists: an updated patent review (2015–2019)
Published in Expert Opinion on Therapeutic Patents, 2020
Chen Cheng, Salman Jabri, Brandon M Taoka, Christopher J Sinz
In another ADA 2018 abstract, Ligand disclosed preclinical studies on the origin of this potentially favorable clinical profile [83]. The key structural difference between LGD-6972 and other GRAs that have advanced to clinical trials is the presence of a sulfonic acid (in the form of taurine amide) where others bear a carboxylic acid derived from β-alanine. Molecular modeling data have led Ligand to hypothesize that LGD-6972 may induce unique conformational changes to the glucagon receptor, which could result in biased signaling. As such, a series of carboxylic acid and the corresponding matched-pair sulfonic acids were tested in cellular models of glucagon-stimulated cAMP accumulation, β-arrestin recruitment, and receptor internalization. The carboxylate GRAs were found to be full antagonists with regard to cAMP, β-arrestin, and receptor internalization. In contrast, sulfonic acid analogues were found to be full antagonists with regard to cAMP, but partial inhibitors of β-arrestin recruitment and receptor internalization. A comparison of the transcriptional effects of MK-0893 vs LGD-6972 in primary hepatocytes treated with glucagon showed what was described as ‘broad differences,’ though details were not disclosed. These results are intriguing and additional studies are eagerly awaited.
Exploring the multiple binding modes of inhibitors to carbonic anhydrases for novel drug discovery
Published in Expert Opinion on Drug Discovery, 2020
For all these CAIs, a heteroatom or a moiety from the inhibitor molecule (e.g. the primary amino group in polyamines, the sulfonic acid in the hydrolyzed sulfocoumarins, exocyclic sulfur in thioxocoumarins or a COOH group in the carboxylic acids) performs the same function as the phenolic OH of 2, i.e. anchoring the inhibitor to the zinc-coordinated water and eventually participating in other H-bond interactions with amino acid residues in the neighborhood, such as for example Thr199/Thr200 (in hCA II, the most investigated isoform) [69–71]. It should be mentioned that the anchoring may be achieved also to the hydroxide bound to Zn(II), not only to the water, since many X-ray crystal structures of such adducts were obtained at pH values at which there should be a significant proportion of zinc hydroxide species of the enzyme [63,69–71]. However, the real protonation state of the water bound to zinc and also of the anchoring moiety of some inhibitors (such as phenols, polyamines, or sulfonic acids) has not been precisely determined by the available techniques used to date [63,69–71]. It should also be mentioned that in all these classes of CAIs, the scaffold also contributes to the formation of a strong enzyme-inhibitor complex, but as already mentioned, the contribution of the scaffold will be discussed in a subsequent paragraph. Detailed computational studies for this type of inhibition were performed for sulfocoumarins [72], which behave as prodrug inhibitors, i.e. are hydrolyzed to sulfonic acids by the sulfatase activity of the enzyme (see also the next inhibition mechanism discussed below). The computational work showed that the rate-determining step of this process is a dual nucleophilic/acidic attack of the active site zinc hydroxide species of the enzyme to the sulfocoumarin sulfur atom and concomitantly to the C3 = C4 double bond of the heterocyclic system [72].
Two sulfonate metabolites of physalin A in rats
Published in Xenobiotica, 2018
Hongxia Liu, Kai Wang, Guiyang Xia, Kun Wang, Liwei Chai, Paul Owusu Donkor, Liqin Ding, Feng Qiu
In conclusion, these results demonstrated that physalin A underwent sulfonate reactions by addition of sulfonic acids to α,β-unsaturated carbonyls to form sulfonate metabolites. This research provided scientific and reliable support for understanding the metabolic types of physalin A in vivo. Sulfonation, a metabolic pathway of physalin A in rats was revealed.