Explore chapters and articles related to this topic
Biochemical Aspects of Fatty Liver
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
CCl4 is the model for a class of halogenated alkanes and alkenes. Several of such compounds, such as CCl4 itself, are extensively used in the solvent industry. Others, such as chloroform, have been used in anesthesiology in the past, and others, such as halothane, are still being used for this purpose. Other haloalkanes, such as 1,2-dibromoethane, are used in agriculture. Therefore, the knowledge of the mechanism of action of such substances has social relevance.
The Effects of Experimental Diabetes on the Cytochrome P450 System and Other Metabolic Pathways
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Costas Ioannides, Peter R. Flatt, Christopher R. Barnett
Compatible with the role of ketone bodies in CYP2E1 induction, the hepatotoxicity of dimethylnitrosamine was potentiated, not only in IDDM rats but also in animals that were subjected to fasting or treated with acetone or isopropanol, which is metabolized to acetone.80 Similarly, the toxicity of haloalkanes, such as carbon tetrachloride, chloroform, 1,1-dichloroethylene, and 1,1,3-trichloroethylene, was potentiated in rats pretreated with acetone or 1,3-butanediol, which induces ketosis by being converted to acetoacetate, acetone, and 3-hydroxybutyrate.105–108 In concordance with the above, the metabolism of chloroform was increased in animals treated with acetone, as a result of an increase in CYP2E1 activity.99 Moreover, hepatic preparations from rats rendered hyperketonemic by the dietary administration of triacylglycerols, like similar preparations from IDDM animals, were more efficient in catalyzing the CYP1A2-mediated bioactivation of Glu-P-1 and Trp-P-2 and the CYP2El-mediated activation of nitrosopiperidine and nitrosopyrrolidine to mutagens in the Ames test.109 The experimental evidence implicating hyperketonemia as an important factor responsible partly for the diabetes-induced changes in hepatic cytochromes P450 is clearly overwhelming. It has been suggested that ketones are converted to fatty acids that may be responsible for the effect of ketones on the cytochrome P450 system, at least in the case of CYP2B.103
Pullulan based derivatives: synthesis, enhanced physicochemical properties, and applications
Published in Drug Delivery, 2022
Surendra Agrawal, Divya Budhwani, Pravina Gurjar, Darshan Telange, Vijay Lambole
Alkylation involves the reaction of pullulan to form alkyl pullulan. It can be synthesized by the pullulan reaction with haloalkane in the presence of NaOH. The degree of substitution of haloalkane is inversely proportional to the glass transition temperature of pullulan, which means the glass transition temperature of pullulan decreases with an increase in the degree of substitution of pullulan. In contrast, an increase in the degree of substitution of haloalkane enhances the solubility in general organic solvents. Alkylated pullulan was prepared using propyl- and butyl-etherified pullulans (PrPL and BuPL), and shows improved solubility in a general organic solvent and resistance from the water (Shibata et al., 2002). Alkyl pullulan has application in modifying substances containing amine, hydroxyl, carboxyl, thiol, or any other group (Mocanu et al., 1999).
Angiogenesis and anti-leukaemia activity of novel indole derivatives as potent colchicine binding site inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yongfang Yao, Tao Huang, Yuyang Wang, Longfei Wang, Siqi Feng, Weyland Cheng, Longhua Yang, Yongtao Duan
The one-step synthetic pathway adopted to prepare 6–9 is depicted in Scheme 1. Different aldehydes reacted with 3′,4′,5′-trimethoxyacetophenone under the presence of NaOH solution resulting in excellent yield of compound 6–9 (synthetic detail procedure is given in the Experimental section). As shown in Scheme 2, the first step to prepare compounds 16–21 was similar to step i above mentioned. Then the intermediates 6, 16–21 and different haloalkanes reacted in the presence of NaH to yield the target compound 23a-29e. DYT-1 was prepared similarly to 6–9 and 16–21. 4-Quinolinecarboxaldehyde reacted with 3′,4′,5′-trimethoxyacetophenone led to DYT-1. Also, we should point out that compounds 622, 23-27a,2628a27 and 29a-d22 ever were reported in our previous research and others. However, these reported compounds never were evaluated for anti-angiogenic activity.
In silico identification and experimental validation of cellular uptake and intracellular labeling by a new cell penetrating peptide derived from CDN1
Published in Drug Delivery, 2021
Xiangli Guo, Linlin Chen, Lidan Wang, Jingping Geng, Tao Wang, Jixiong Hu, Jason Li, Changbai Liu, Hu Wang
HaloTag, a type of self-labeling protein tag, is a modified haloalkane dehalogenase derived from a bacterial enzyme. Containing 297 amino acids (33 kDa) (England et al., 2015), it cannot pass through the cell membrane without a transport vector. Data shown in this paper suggest that peptide P2 is an alternative CPP for potential macromolecule delivery. We constructed the HaloTag-P2 fusion expression plasmid, and we induced its expression and purified fusion protein via a prokaryotic protein expression system (Figure 7(A)). We also prepared protein HaloTag and HaloTag-Dot1l (a CPP found by our group (Geng et al., 2020)) as control (Figure 7(A)). Then, we followed our protocol shown in Figure 7(B) to treat HepG2 and HeLa cells. After substrate TMR incubation and washing, fluorescence images were captured. As shown in Figure 7(C,D), Figure S8(A–C), a very low amount of (0.25 µg/ml or 0.4 µg/ml protein) peptide P2 fused with HaloTag can be delivered into intracellular and cell nucleus, but the groups of TMR substrate only and HaloTag protein only do not have any signaling in the cell. These results suggest that peptide P2 not only can penetrate culture cell lines but also can deliver macromolecules like self-labeling HaloTag into cells.