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Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
One of the most widely studied compounds is triparanol (4-chloro-α-[4-[2-〈diethylamino〉ethoxy]phenyl]-〈4-methylphenyl〉benzeneethanol, MER-29).17,71,192 Triparanol lowers blood cholesterol by inhibiting 75% or more of the endogenous synthesis. It blocks the reduction of the 24, 25 double bond in the steroid side chain, leading to the accumulation of 25-dehydrocholesterol, as it is commonly known, desmosterol.627 Desmosterol replaces cholesterol in lipoproteins, and therefore, triparanol therapy leads to the accumulation of the precursor compound in the blood in place of cholesterol. The lipoprotein pattern returns to normal in Type II patients but not in Type IV. Probucol has no consistent action on lipogenesis in experiments, but apparently decreases endogenous cholesterol synthesis and intestinal reabsorption.
Phytosteroids and Related Compounds
Published in Amritpal Singh Saroya, Contemporary Phytomedicines, 2017
Desmosterol, 24,25-epoxycholesterol, 24-hydroperoxycholesta-5,25-dien-3 beta-ol, 25-hydroperoxycholesta-5,23(E)-dien-3 beta-ol, cholesta-5,25-diene-3 beta,24-diol, and 24,25-epoxy-6 beta-hydroxycholest-4-en-3-one) were isolated. Sterols exhibited significant cytotoxicity toward several cancer cell lines (Sheu et al. 1996).
The old world salsola as a source of valuable secondary metabolites endowed with diverse pharmacological activities: a review
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mai H. ElNaggar, Wagdy M. Eldehna, Mohammed A. S. Abourehab, Fatma M. Abdel Bar
Steroids are a group of natural products biosynthesized from the isoprenoid pathway via the 2,3-oxidosqualene (C30) route. Cardenolides are cardioactive steroidal lactones with a 5-membered (furanones) or 6-membered (pyranone) ring at C-17. They are naturally present free or glycosylated with mono- or multi-sugar moieties. Several families are known for their high cardenolides content, such as Asclepidaceae, Apocynaceae, and others72. However, only one report on cardenolides from the Amaranthaceae family has been described. It addressed the isolation of five cardenolides, salsotetragonin 2.1, calactin 2.2, 12-dehydroxyghalakinoside 2.3, desglucouzarin 2.4, and uzarigenin 2.5 from the Algerian plant, Salsola tetragona Delile, Figure 350. Other reported steroids comprised several phytosterols with diversity in the alkyl side chains at C-17, including campesterol 2.6, cholesterol 2.7, and desmosterol 2.8 from S. collina73, β-sitosterol 2.9, stigmastanol 2.10, and stigmasterol 2.11, in addition to a combined phytosterol, stigmasterol-3-O-β-D-glucopyranoside 2.12 from the aerial parts of S. inermis51.
Statins significantly repress rotavirus replication through downregulation of cholesterol synthesis
Published in Gut Microbes, 2021
Shihao Ding, Bingting Yu, Anneke J. van Vuuren
U18666A is an inhibitor that targets desmosterol reductase and sterol–D8–D7 isomerase and oxidosqualene cyclase (OSC) in the mevalonate pathway to specifically block cholesterol production.33 By 1.25 µM U18666A treatment, the intra- and extracellular rotavirus RNA copies were summarized by qRT-PCR analysis in Caco2 cells (Figure 4e). U18666A dropped the intra- and extracellular virus RNA to around 40% similarly. Moreover, there were also significant decreases in the rotavirus VP4 and VP6 proteins (Figure 4e, Figure S2c, Figure 5e). In MA104 cells, U18666A showed the decreases to 26% and 38% of rotavirus RNA copies in the intra- and extracellular respectively, and the western blotting and IF staining results further confirmed that (Figure 4f, Figure S2c, Figure S5f). As shown in Figure 4i and k, Figure S2c, Figure 5g, U18666A suppressed rotavirus replication in HSI organoids. These results revealed that the decrease of cholesterol production repressed rotavirus replication.
Drug development for Alzheimer’s disease: review
Published in Journal of Drug Targeting, 2019
Kejing Lao, Naichun Ji, Xiaohua Zhang, Wenwei Qiao, Zhishu Tang, Xingchun Gou
Non-carboxylic acid GSMs have been inspired by the work of the Eisai group and their discovery of very important GSMs in 2005. E2012 (13) was shown to be a potent early GSM (EC50 = 83 nM) and was the first non-carboxylic acid GSM to enter clinical trials in 2006 [43]. While the Phase 1 studies demonstrated dose-dependent plasma reductions of Aβ42, it was found that it inhibits 24-dehydrocholesterolreductase leading to increased desmosterol and decreased cholesterol in the lens, which ultimately produce cataracts [44]. Thus, Eisai decided to develop its anaolog E2212 (14) instead. In a phase 1 clinical trial, E2212 was demonstrated to be safe and well tolerated with 54% Aβ42 reduction [45]. Until recently, no further development of E2212 has been reported, and there remained much need to optimise the drug-like properties after this initial effort to develop GSMs.