China
Africa
Explore chapters and articles related to this topic
Toward Clinical Pharmacologic Otoprotection
Published in Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm, Advances in Audiology and Hearing Science, 2020
Colleen G. Le Prell, Kelly Roth, Kathleen C. M. Campbell
Methionine is an important amino acid typically obtained from protein sources such as meats, dairy products, and beans, nuts and seeds. Methionine promotes the re-synthesis of glutathione (GSH) in response to GSH depletion (Morris et al., 2014) and serves as an antioxidant (Kim et al., 2014; Morris et al., 2014). Like most nutritionally important amino acids, D-methionine (D-Met), and L-methionine (L-Met) are mirror images, termed enantiomers, and they differ based on the presence of one asymmetric carbon atom (Friedman, 1999). Like other protein-associated D-amino acids, the D-Met enantiomer is more poorly absorbed than the L-isomer (Friedman and Levin, 2012; Zhang et al., 2015). D-isomers may, therefore, be better candidates for delivery in fortified foods (Friedman and Levin, 2012).
Narcotic Analgesics And Antagonists
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
The acetylmethadols, exemplified by Formula 24, are obtained by acetylation of the reduction products of methadone. The formation of a new asymmetric carbon atom leads to additional isomers. Alpha-i-acetylmethadol can be obtained by a lithium aluminum hydride reduction of d-methadone, and subsequent acetylation of the newly formed secondary alcohol; the prefix alpha referring to the predominant product obtained. Chemical reduction of methadones (via sodium in propanol) gives, predominantly, d-betamethadol.41
Special Problems in Structures of Drugs
Published in Joseph Chamberlain, The Analysis of Drugs in Biological Fluids, 2018
The first edition of this work was like similar works of its period in that it gave only scant attention to the chiral nature of some drugs, or to the fact that almost all synthesized drugs which had an asymmetric carbon were marketed as racemates. Workers in the field must have been aware of such things; after all, molecular asymmetry had been studied widely in the middle of the nineteenth century. The whole basis of organic chemical structure is based on the tetrahedral carbon atom and the concept of mirror-image isomers is an inevitable consequence. Many of the synthetic drugs initially produced by the pharmaceutical industry were semisynthetic and based on naturally occurring precursors such as steroids and β-lactams. Fortuitously, the marketed compounds were optically pure, and any consideration of enantiomeric forms of the drug did not normally arise.
Tripeptides conjugated with thiosemicarbazones: new inhibitors of tyrosinase for cosmeceutical use
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Patrycja Ledwoń, Waldemar Goldeman, Katarzyna Hałdys, Michał Jewgiński, Greta Calamai, Joanna Rossowska, Anna Maria Papini, Paolo Rovero, Rafał Latajka
Understanding the nature ofguest–host interactions is mandatory for the rational design of inhibitors. Molecular modelling, especially simulation of the docking process, can contribute to understanding the physical nature of those interactions. Performing docking simulations allow us to better understand the results of biological tests. During the preliminary steps, structures of the investigated thiosemicarbazones and their conjugates with the designed tripeptide sequences have been optimised by using Gaussian16 code at the B3LYP/6-311g(d,p) level with a solvent model and water as solvents. In the case of TSC 2, containing an asymmetric carbon atom, both R and S isomers have been considered. Isomer E was docked as the default configuration, however during the docking process there was a possibility to freely change between E and Z. No significant results were found for Z isomer; therefore, all the presented data refer to the preferential E configuration. In the second preliminary step, the structure of tyrosinase was protonated at pH 6.8 using H++ web server54,.55 Tyrosinase structure has been obtained from Protein Data Bank (PDB ID: 2Y9X).53 Calculated structures of inhibitors were docked to the active site of tyrosinase by using Gold ver. 2021.3 algorithm.65 Ten orientations of each investigated inhibitor were obtained, among which the ones with the best value of the ChemPLP scoring function were selected for further investigations.
Menthol additives to tobacco products. Reasons for withdrawing mentholated cigarettes in European Union on 20th may 2020 according to tobacco products directive (2014/40/EU)
Published in Toxicology Mechanisms and Methods, 2020
Paulina Natalia Kopa, Rafał Pawliczak
Menthol (cyclohexanol-5-methyl2-(1-methylethyl); C10H20O (Figure 1) is a natural cyclic monoterpene alcohol with a minty smell and cooling properties. It is one of the main constituents of essential oils, which are naturally present in some aromatic plants, such as Mentha × piperita L, and it may also be synthesized on a commercial scale (Werley et al. 2007; Kamatou et al. 2013). Based on its structure, menthol may occur in four pairs of optical isomers, due to three asymmetric carbon atoms situated in cyclohexane ring (Ahijevych and Garrett 2004; Werley et al. 2007). Menthol is used in a variety of merchandises, such as food (i.e. chocolate, chewing gum), oral-care products (i.e. toothpaste, mouthwash), OTC products (with local cooling and analgesic effect), cosmetics (increase the dermal penetration of medicaments) and tobacco products (cool sensation and reduction of smoking harshness effect) (Kamatou et al. 2013; Ton et al. 2015). In addition, menthol shows anesthetic, analgesic, antibacterial and antifungal, immunomodulating, and skin penetration-enhancing properties (Hoffman 2011; Ton et al. 2015; Thompson et al. 2018).
Comparative toxicity and toxicokinetic studies of oxiracetam and (S)-oxiracetam in dogs
Published in Xenobiotica, 2019
Tian-tian Liu, Xin-miao Guo, Zu-yuan Rong, Xiang-feng Ye, Jin-feng Wei, Ai-ping Wang, Hong-tao Jin
It has been more than twenty years since the discovery of oxiracetam (ORT, 4-hydroxy-2-oxo-1-pyrrolidine acetamide), a derivative of piracetam, which is a nootropic used for treating memory decline and various cognitive function disorders (Bottini et al., 1992; Mondadori et al., 1996; Nicholson, 1990; Villardita et al., 1992). Oxiracetam has also been associated with promising central nervous system protective effects, including in cerebrovascular impairment (Kometani et al., 1991), ischemic stroke(Wang et al., 2014), and brain injury(Yi et al., 2016). Recent studies have shown that oxiracetam can reduce cognitive injury at high altitude (Hu et al., 2017; Li et al., 2017) and was selected to be co-administered with nerve growth factor for the treatment of hypertensive cerebral hemorrhage (Sun et al., 2018). Oxiracetam has an asymmetric carbon, and its enantiomers are (S) -and (R)-ORT (Figure 1). It is used as a racemic mixture in clinical treatment. Studies have shown that (S)-ORT has high efficacy and is the active component of racemic oxiracetam (Fan et al., 2018; Li et al., 2017). To the best of our knowledge, most studies have focused on differences in the effects of ORT enantiomers from a pharmacological (Baumann & Eap, 2001; Kasprzyk-Hordern, 2010) or pharmacokinetic (Son et al., 2004; Wan et al., 2014; Zhang et al., 2015a) perspective. However, the in vivo toxicity and toxicokinetics of oral ORT and (S)-ORT have not yet been investigated. Accordingly, ORT and (S)-ORT were evaluated in acute and 90-day repeated-dose toxicity and toxicokinetic studies in dogs following oral exposure, as described herein.