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The Isolated Hepatocyte and Isolated Perfused Liver as Models for Studying Drug- and Chemical-Induced Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
David J. Sweeny, Robert B. Diasio
A major application of the isolated perfused liver is that the model can be used in studying the mechanism by which a variety of compounds produce toxicity to specific zones of the liver lobule. As an example, allyl alcohol has been shown to produce periportal toxicity following in vivo administration to rats (Piazza, 1915). This toxicity is dependent on the metabolism of allyl alcohol by alcohol dehydrogenase, since the allyl alcohol-induced hepatotoxicity can be prevented by the prior administration of pyrazole, an inhibitor of alcohol dehydrogenase (Reid, 1972). It has been suggested that allyl alcohol-induced periportal toxicity results from preferential metabolism in this region of the liver lobule, since histochemical evidence indicated that periportal hepatocytes contained higher levels of alcohol dehydrogenase than pericentral hepatocytes (Reid, 1972). However, analysis of the zonal distribution of alcohol dehydrogenase utilizing a microchemical assay had earlier demonstrated that alcohol dehydrogenase activity was greater in hepatocytes located in centrilobular rather than periportal regions of the liver lobule (Morrison and Brock, 1967). Moreover, the contention that periportal toxicity results from preferential metabolism allyl alcohol in this region of the liver lobule may be further questioned, since in the intact cell alcohol dehydrogenase activity may be regulated by the availability of NAD+ (Kashiwagi et al., 1982), which is uniformly distributed across the liver lobule (Matschinsky et al., 1978).
Manufacture of Glycerine from Petrochemical and Carbohydrate Raw Materials
Published in Eric Jungermann, Norman O.V. Sonntag, Glycerine, 2018
The distilled allyl alcohol is oxidized with a 2 M aqueous solution of H2O2 containing 0.2% tungstic oxide. The glycerol water mixture, which is generated within 2 hr reaction time at 60–70°C is distilled to afford high-purity glycerol. The filtered catalyst is recycled. Yield of glycerol (based on allyl alcohol) is 80–90%; the overall yield of glycerol based on propylene is about 50%. Isopropanol and hydrogen peroxide auxiliary raw materials can be produced from propylene; acetone is highly marketable.
Linkers in fragment-based drug design: an overview of the literature
Published in Expert Opinion on Drug Discovery, 2023
Dylan Grenier, Solène Audebert, Jordane Preto, Jean-François Guichou, Isabelle Krimm
The ether function is also widely used in medicinal chemistry due to its high stability. Two main reactions give access to ether derivatives, the Mitsunobu and the Williamson reactions. Szczepankiewicz et al. [19] linked two fragments with amide and ether functions, leading to the discovery of protein PTP1B inhibitors. One of the fragments carried a carboxylic acid function while the second, a naphthoic acid, had to be functionalized. A Mitsunobu reaction was used to obtain the ether linker containing a primary amine. Finally, the combination of the acid and amine fragments resulted in a 22 nM PTP1B inhibitor. For the same target, Liu et al. [20] combined two fragments with a more rigid linker (allyl ether) than usual. One fragment was modified by a Still coupling reaction to introduce an allyl alcohol function. The modified fragment was linked to the second fragment containing a phenolic function using a Mitsunobu reaction. A lead compound with an IC50 of 6.9 µM was obtained.
Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yuan Gao, Nian-Dong Mao, Hao Che, Li Xu, Renren Bai, Li-Wei Wang, Xiang-Yang Ye, Tian Xie
The interesting biological activities and the easy accessibility of novel compound 11a encouraged us to investigate more on N-alkyl-N-hydroxyl carboximate class analogs of β-elemene. In order to accomplish the work, we first needed to prepare 13-Br-β-elemene (4) in a workable amount (Scheme 1). Compound 4 was previously prepared from the corresponding allylic alcohol by Xu et al.19 using NBS/Ph3P condition. This route not only added one extra step of alcohol preparation but also required tedious separation of close related isomer in allylic alcohols. We worked out an alternative route of direct bromination at the 13-position (one of the allylic positions) of 1. By following the procedure in our patent application25, compound 4 was prepared in 30.1% yield with good purity, enough for the next step displacement reaction. The minor isomer 14-Br-β-elemene (6) did not interfere with the following step reaction.
Antifouling properties of amphiphilic poly(3-hydroxyalkanoate): an environmentally-friendly coating
Published in Biofouling, 2021
A. Guennec, L. Brelle, E. Balnois, I. Linossier, E. Renard, V. Langlois, F. Faÿ, G. Q. Chen, C. Simon-Colin, K. Vallée-Réhel
Unsaturated PHBHHx oligomer was obtained according to the procedure described by Ramier et al. (2012). PHBHHx (1g) was solubilized in anhydrous chloroform (10 ml) and 9.3.10−3 moles of allyl alcohol and DBTL with a molar ratio nOH/nDBTL = 34 were added. The reaction was carried out in an Anton-Paar monowave 300, MW reactor. The MW source was a magnetron with a 2.5 GHz frequency (850W power generator). The sample was heated at 160 °C for 15 min. The oligomers were finally precipitated in 100 ml of n-pentane and dried under vacuum at 40 °C (Yield 91%). Unsaturated PHBHHx was solubilized in DMSO (60 g l−1). 2.5eq molar of PEGSH was added in presence of 2 molar equivalents of DMPA. The mixture was irradiated at 100% for 30 min under agitation with the Hamamatsu lightening cure LC8 (L8251), equipped with a Mercury-Xenon lamp (200 W) coupled with a flexible light guide. The process from the addition of PEGSH and DMPA was repeated twice. The copolymer was then placed in 50 ml of DMF and purified twice by dialysis over 15 days by changing the water every 2 h.