China
Africa
Explore chapters and articles related to this topic
History and Sources of Essential Oil Research
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Diastereomeric association between chiral molecules and chiral transition metal complexes was first described by Schurig (1977). Since hydrogen bonding interaction is not essential for chiral recognition in such a system, a number of compounds could be separated, but this method was limited by the nonsufficient thermal stability of the applied metal complexes.
Chemical Hybridization Approaches Applied to Natural and Synthetic Compounds for the Discovery of Drugs Active Against Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Elena Petricci, Paolo Governa, Fabrizio Manetti
The impact of the stereochemistry in the activity of 68 was also evaluated even if no indication was reported about the stereoselective synthesis and the purification of the racemic mixture. It is interesting to note that the stereochemistry affected toxicity, as 68a was significantly more toxic than its diasteroisomer 68b (Figure 17). Cytotoxic effects of 68a and 68b on L. donovani promastigotes. (a) Schematic representation of the structure of the diastereomers. (b) (Adapted from Ramu et al. 2017). Compound 68a exerted toxic effects on L. donovani promastigotes. Cytotoxic effect of 68a and 68b was evaluated using LDH Assay (post 72 h, conc.: 1–100 μM). Inhibition was calculated by taking the cytotoxicity of positive control (2.5 μg/mL amphotericin B) as 100% for normalization. (c) (Adapted from Ramu et al. 2017). Non-toxic effect of 68b on L. donovani promastigotes. Long-term effect on promastigotes survival with 68b exposure was examined by evaluation of cytotoxicity on parasites for 9 days following its addition.
B
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Boceprevir is administered as an approximately equal mixture of two diastereomers which rapidly interconvert in plasma. At steady-state, the exposure ratio for the two diastereomers is approximately 2:1, with the predominant diastereomer being pharmacologically active.
In vitro hepatic metabolism of the natural product quebecol
Published in Xenobiotica, 2023
Although the 3-position of the propanol substituted with the 3-methoxy, 4-hydroxy phenyl groups is not chiral, glucuronide substitution of either phenol would create a chiral centre and therefore a novel stereoisomer. This results in the potential formation of six glucuronide stereoisomers (Figure 9. R; S; R,R; S,S; R,S; S,R). While it is tempting to assume that these result in 3 enantiomeric pairs (R and S; R,R and S,S; R,S and S,R), glucuronic acid is also chiral, but is only present in the D-glucuronic acid form so that none of the stereoisomers are mirror images (enantiomers) and therefore all of the possible phenol glucuronide conjugates are diastereomers. Diastereomers can frequently be separated by HPLC in the absence of a chiral column. The three distinct glucuronide signals in the HPLC (Figure 4) suggests to us that at least three phenol stereoisomers are present. It is possible that all 6 stereoisomers are present in our incubation as the different pairs of isomers (R,S), (R,R; S,S) and (R,S; S,R) may be poorly resolved by non-chiral HPLC and co-elute. It should also be noted however that enzymatic selectivity for the formation of specific glucuronide isomers remains a possibility. However, the ESI-MS/MS fragmentation did not allow us to distinguish between the stereoisomers as fragmentation leading to loss of the glucuronide (MW 176.2) occurred for all three metabolites.
GPR119 agonists for the treatment of type 2 diabetes: an updated patent review (2014-present)
Published in Expert Opinion on Therapeutic Patents, 2021
Huilan Li, Yuanying Fang, Shuchun Guo, Zunhua Yang
Hyundai Pharm. reported a class of piperazine compounds as GPR119 activators for preventing or treating obesity and diabetes in the patent WO2014077532 [59]. Among them, 39 and 40 (Figure 7) had the same chemical structure, while the pure enantiomer 40 showed better EC50 than the diastereomer mixture 39. More importantly, 39 and 40 displayed stronger blood glucose lowering effect than MBX-2982 in male C57BL/6 J rats (18.6%, 16.2% vs 14.7%, respectively). Afterward, they published a series of novel cyclohexene derivatives 41–47 for treatment metabolic disease by activating GPR119 in the patent WO2017078352 [60]. 41–47 exhibited very potent GPR119 agonistic activities and the EC50s are less than 10 nM except 41 (Table 3). However, compound 41 bearing (R)-1-hydroxy-2-propylcarbamoyl group was revealed to show the best blood glucose deceasing efficacy by 28.5% in oGTT.
Effects of vitamin K1 treatment on plasma concentrations of long-acting anticoagulant rodenticide enantiomers following inhalation of contaminated synthetic cannabinoids
Published in Clinical Toxicology, 2020
Douglas L Feinstein, Daniel G Nosal, Swetha Ramanathan, Jifang Zhou, Luying Chen, Ronald C Hershow, Richard B van Breemen, Erik Wright, John W Hafner, Israel Rubinstein
The chemical structures of BDF, DiF, BDL, and BDF-d4 are shown in Figure 1(A). Each contains two chiral centers (represented by wavy lines) resulting in two diastereomer pairs. Diastereoisomeric separations of BDF and DiF (Figure 1(B)) were carried out using a Shimadzu (Kyoto, Japan) LCMS-8060 triple-quadrupole mass spectrometer equipped with a Shimadzu Nexera chromatography system and an Agilent (Santa Clara, CA, USA) Poroshell EC-C8 (50 × 2.1 mm i.d., 2.7 µm) column. The solvent system consisted of water (A) and acetonitrile (B) both containing 0.01% formic acid. A linear gradient from 40% to 75% B over 3 min was used followed by 95% B for 0.9 min and re-equilibration at 40% B for 1.6 min. The flow rate was 0.6 mL/min. The injection volume was 10 μL and the column temperature was 50 °C. Negative ion electrospray, collision-induced dissociation, and selected reaction monitoring (SRM) of both quantifier and qualifier transitions were used for LC-MS/MS quantitative analysis of each LAAR. Calibration curves for cis-/trans-BDF, cis-/trans-DiF, and BDL were plotted using exponential curve fitting (R2 > 0.998) and a low limit of quantitation (LLOQ) between 0.125 and 0.63 ng/mLm depending on the LAAR. Ratios of cis- to trans-diastereoisomer pairs were determined by summing both mass chromatographic peak areas and dividing by the peak area of a single diastereoisomer pair. This protocol did not allow the separation of BDL into its diastereomeric pairs.