Food Interactions, Sirtuins, Genes, Homeostasis, and General Discussion
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
It is noteworthy that most nutrients such as proteins, enzymes, amino acids, carbohydrates, nucleosides, antioxidants, and vitamins in animal and plant organisms are chiral compounds, and exist under single stereoisomer form only. For example, all natural amino acids are l-isomer (levorotatory) and all natural sugars (carbohydrates) are d-isomer (dextrorotatory). The same chiral artificial products obtained by chemical synthesis are often under racemic form – a mixture of two stereoisomers, such as d-isomer and l-isomer, S- and R-enantiomers, or cis- and trans-isomers. Our body is a great factory of chiral selectors, and could well distinguish the stereoform of a biological compound. Although they have the same chemical structure, most enantiomers of racemic products exhibit marked differences in biological activities such as pharmacology, toxicology, pharmacokinetics, and metabolism. That means our organism is smart enough to differentiate between ‘good’ and ‘bad’ isomers present, although both isomers have the same apparent chemical structure (147). That is why some chiral dietary supplements obtained by chemical synthesis do not have the same biological or therapeutic properties as their corresponding natural compounds present in foods.
Immunomodulatory Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
It is noteworthy that thalidomide is synthesized, purified, and administered as a racemic mixture. However, the individual (R)- and (S)-enantiomers differ from the racemate, each having higher water solubility by a factor of approximately three. There is also indirect evidence that enantiomerically pure thalidomide is absorbed more readily and undergoes faster hydrolytic cleavage. Another interesting aspect of the stereochemistry is that the (R)-enantiomer is responsible for the sedative effect, whereas the (S)-isomer is teratogenic. However, both in vitro and in vivo studies have shown that, under physiological conditions, there is very rapid racemization, so whichever enantiomer is administered, a similar equilibrium mixture will quickly be established.
Rationale and technique of malaria control
David A Warrell, Herbert M Gilles in Essential Malariology, 2017
Its chemical constitution is remarkably simple (C6H6C16), because it consists of a benzene ring with a chlorine atom attached to each carbon. The arrangement of the hydrogen and carbon atoms in space may vary, so that a number of optical isomers exist, the most active of which is the gamma isomer. This isomer, when pure, or at least 99 per cent pure, is called lindane. Technical HCH must contain at least 12 per cent of the gamma isomer. It is soluble in organic solvents, and is a whitish or light-brown, granular or flaky substance with a characteristic musty smell. It is relatively volatile and may kill insects fairly rapidly by fumigant action. However, because of this volatility, its residual action is generally half as long as that of DDT, although its toxic action is faster. It is classed as a moderately hazardous insecticide, with an LD50 of 100 g/kg based on the cumulative properties of the beta isomer. HCH may be used in the form of a water-dispersible powder, containing 6.5 per cent gamma isomer, as a residual insecticide for indoor spraying of walls; other formulations (solutions, emulsions) exist for use as larvicides or as insecticidal smoke. The usual dosage of HCH for residual spraying is 0.3 g/m2 every 3 months or 0.5 g/m2 every 4–6 months.
Glutaminase inhibitors: a patent review
Published in Expert Opinion on Therapeutic Patents, 2018
CanRong Wu, LiXia Chen, Sanshan Jin, Hua Li
As shown in Figure 5, these compounds exhibited IC50 values between 20 and 100 nM. In addition, the inhibition potency of these compounds on human lung squamous cell NCI-H1703 proliferation was presented in Figure 6. All those six compounds showed high inhibition efficiency in cancer cell proliferation with IC50 in low nanomolar scale. The lead compounds derived from these above synthesized compounds were not mentioned in the patent. The other type of compounds in patent WO2017093299 described in formulae 7a and 7b. Q represented l,2,4-triazin-3-yl, 6-methylpyridazin-3-yl, 6-fluoropyridazin-3-yl or pyridazin-3-yl; R1 could be hydrogen, methoxyl, trifluoromethoxyl, 3-fluoroazetidin-l-yl, oxetan-3-yl, 3,3-difluoroazetidin-l-yl or 3-methoxyazetidin-l-yl; R2 was methoxy, ethoxy or methoxymethyl; R3 represented hydrogen or fluoro; and R4 was hydrogen or methoxy. A part of the compoundsis displayed in Figure 6, for example, compounds 22a and 22b are a pair of isomer when their substituents are the same. Interestingly, most of the synthesized compound conforming to formula 7a showed more potent inhibition on enzyme and cell proliferation compared to its isomers derived from formula 7b. Among all these compounds, compound 25a (Table 3), in which R1, R2, R4 are methoxyl; R3 is hydrogen; and Q is pyridazin-3-yl, showed the most significant inhibition activity in enzyme and cell proliferation.
Fibrate-based N-acylsulphonamides targeting carbonic anhydrases: synthesis, biochemical evaluation, and docking studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Alessandra Ammazzalorso, Simone Carradori, Andrea Angeli, Atilla Akdemir, Barbara De Filippis, Marialuigia Fantacuzzi, Letizia Giampietro, Cristina Maccallini, Rosa Amoroso, Claudiu T. Supuran
Docked poses have been identified in which the ligands directly interact with the zinc-bound water molecule. For example, the R isomer of compound 1 forms a hydrogen bond with the water molecule through its sulphonamide oxygen atom (Figure 2(C)). The carbonyl group of the ligand forms a hydrogen bond with the side chain of Gln92. A third hydrogen bond is formed between the ligand and the side chain of Trp5. The propyl group of the ligand is located in a hydrophobic pocket formed by Val62, His64, His67, and His200. The phenyl group of the ligand forms hydrophobic interactions with Phe91, Leu131, Leu141, and Leu198. Interestingly, similar docked poses have not been obtained for the S isomer of compound 1. Similar observations have been made for the other compounds in which some isoforms may bind to one stereoisomer but not to the other.
An update on liposomes in drug delivery: a patent review (2014-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Mazen M. El-Hammadi, José L. Arias
Light can also be employed as a physical stimulus to trigger and control the release of active ingredients from LPs. In clinical applications, activating photons must safely cross the biological tissues without absorption and be absorbed only by the LP components to trigger the release process. Light in the near infra-red (NIR) range of the spectrum (700 to 1100 nm) is of particular interest because it is transmissible deep into human tissue owing to limited scattering and little absorption coefficients [82]. Light-initiated reactions induce localized increase in membrane permeability via either reversible conformational changes or irreversible modification in the components comprising the vesicle [83]. In this line, LPs comprising azobenzene derivatives in the lipid bilayer can achieve the controlled release of the encapsulated drug through ultraviolet (UV) irradiation [84,85]. Azobenzene is composed of two phenyl rings linked by an N= N double and can transform the trans-isomer into the cis-isomer under UV light. The reversible isomerization of the azo-groups caused by UV light destabilizes the liposomal membrane, leading to drug release.
Related Knowledge Centers
- Diastereomer
- Functional Group
- Oleic Acid
- Stereoisomerism
- Substituent
- Descriptor
- Conformational Isomerism
- But-2-Ene
- Chemical Polarity
- Pentene