5672-71-9Relevant academic research and scientific papers
Synthesis of rationally designed mechanism-bsed inactivators of the (S)-adenosyl-L-methionine: Δ(24(25))-sterol methyl transferase
Jia, Zhonghua,Zhou, Wen,Guo, Dean,Nes, W. David
, p. 3841 - 3848 (1996)
A series of 26,27-cyclopropylidine side chain modified sterols were prepared for the first time from the known aldehydes by Wittig olefination with the ylide from cyclopropyltriphenylphosphonium bromide in butyllithium. Two novel by-products were detected; sterols with nine carbon side chains which lack the terminal isopropyl group and with double bonds in positions 23,24 or 24,25. The structures of the compounds were confirmed by a combination of chromatographic (GLC and HPLC) and spectral (IR, 1H, 13C-NMR) methods.
Luciferase-based HMG-CoA reductase degradation assay for activity and selectivity profiling of oxy(lano)sterols
Sagimori, Ikuya,Yoshioka, Hiromasa,Hashimoto, Yuichi,Ohgane, Kenji
, (2020)
HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is the target of cholesterol-lowering drugs, statins. Previous studies have demonstrated that the enzyme activity is regulated by sterol-induced degradation in addition to transcriptional regulation through sterol-regulatory-element-binding proteins (SREBPs). While 25-hydroxycholesterol induces both HMGCR degradation and SREBP inhibition in a nonselective manner, lanosterol selectively induces HMGCR degradation. Here, to clarify the structural determinants of selectivity for the two activities, we established a luciferase-based assay monitoring HMGCR degradation and used it to profile the structure-activity/selectivity relationships of oxysterols and (oxy)lanosterols. We identified several sterols that selectively induce HMGCR degradation and one sterol, 25-hydroxycholest-4-en-3-one, that selectively inhibits the SREBP pathway. These results should be helpful in designing more potent and selective HMGCR degraders.
Synthesis of Lanostane-Type Triterpenoid N-Glycosides and Their Cytotoxicity against Human Cancer Cell Lines
Ukiya, Motohiko,Hayakawa, Teppei,Okazaki, Kouta,Hikawa, Maiko,Akazawa, Hiroyuki,Li, Wei,Koike, Kazuo,Fukatsu, Makoto
, (2018/07/13)
Seventeen lanostane-type triterpenoid derivatives (2 – 18), including 11N-glycosides (8 – 18), were synthesized from the natural triterpenoid, lanosterol (1), and were evaluated for their cytotoxicity against the human cancer cell lines, HL-60, A549, and MKN45, as well as the normal human lung cells, WI-38. Among them, N-β-d-2-acetamido-2-deoxyglucoside (10) showed cytotoxicity against HL-60, A549, MKN45, and WI-38 cells (IC50 0.0078 – 2.8 μm). However, N-β-d-galactoside (12) showed cytotoxicity against HL-60 and MKN45 cells (IC50 0.0021 – 4.0 μm), but not the normal WI-38 cells. Furthermore, Western blot analysis suggested that 12 induces apoptosis by activation of caspases-3, 8, and 9. These results will be useful for the synthesis of other tetracyclic triterpenoids or steroid N-glycosides to increase their cytotoxicity and apoptosis-inducing activities.
Synthesis, Evaluation, and Structure-Activity Relationship Study of Lanosterol Derivatives to Reverse Mutant-Crystallin-Induced Protein Aggregation
Yang, Xinglin,Chen, Xiang-Jun,Yang, Zimo,Xi, Yi-Bo,Wang, Liguo,Wu, Yue,Yan, Yong-Bin,Rao, Yu
, p. 8693 - 8706 (2018/10/05)
We describe here the development of potent synthetic analogues of the naturally occurring triterpenoid lanosterol to reverse protein aggregation in cataracts. Lanosterol showed superiority to other scaffolds in terms of efficacy and generality in previous studies. Various modified lanosterol derivatives were synthesized via modification of the side chain, ring A, ring B, and ring C. Evaluation of these synthetic analogues draws a clear picture for SAR. In particular, hydroxylation of the 25-position in the side chain profoundly improved the potency, and 2-fluorination further enhanced the biological activity. This work also revealed that synthetic lanosterol analogues could reverse multiple types of mutant-crystallin aggregates in cell models with excellent potency and efficacy. Notably, lanosterol analogues have no cytotoxicity but can improve the viability of the HLE-B3 cell line. Furthermore, representative compound 6 successfully redissolved the aggregated crystallin proteins from the amyloid-like fibrils in a concentration-dependent manner.
Synthesis and bioactivities of steroid derivatives as antifungal agents
Chung, Sung-Kee,Ryoo, Chung Hwan,Yang, Hong Woon,Shim, Jeung-Yeop,Kang, Myung Goo,Lee, Ki Wha,King, Heui Il
, p. 15899 - 15914 (2007/10/03)
A series of lanosterol and cholesterol derivatives with modified side chain structures, which might interfere with sterol C24-methyltransferase in the ergosterol biosynthesis as substrate analogs, have been synthesized. The in vitro bioassay studies have shown that some of these compounds, in particular with C24-amino- and thio-functionalities, possess potent antifungal activities. in vivo. Bioassays have also been carried out for the leading compounds.
