2671-68-3Relevant articles and documents
Trypanosome and animal lanosterol synthases use different catalytic motifs.
Joubert,Buckner,Matsuda
, p. 1957 - 1960 (2001)
[see reaction]. Animals, fungi, and some protozoa convert oxidosqualene to lanosterol in the ring-forming reaction in sterol biosynthesis. The Trypanosoma cruzi lanosterol synthase has now been cloned. The sequence shares with the T. brucei lanosterol synthase a tyrosine substitution for the catalytically important active-site threonine found in animal and fungal lanosterol synthases.
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.
Anticancer compound and use thereof
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Paragraph 0084; 0085; 0086, (2017/06/27)
The invention relates to an anticancer medicine which is a lanosterol derivative. The compound has an anticancer effect, and can inhibit the growths of lung cancer cells, liver cells, mammary gland cells, brain cancer cells, and pancreatic cancer cells. The medicine is a compound with a general formula of (I), (II), (III), or (IV). The invention also provides an application of the compound or pharmaceutically acceptable salt thereof in preparing medicines used for treating cancers. The medicine can be used independently, and can be used in combination. Especially, the medicine can be used in combination with gemcitabine or nexavar. The medicine can be used in treating cancers such as lung cancer, liver cancer, pancreatic cancer, breast cancer, brain cancer, and the like.
Total Synthesis of Echinoside A, a Representative Triterpene Glycoside of Sea Cucumbers
Chen, Xiaoping,Shao, Xiaofei,Li, Wei,Zhang, Xiaheng,Yu, Biao
supporting information, p. 7648 - 7652 (2017/06/13)
Echinoside A, a sulfonylated holostane tetrasaccharide with potent anticancer and antifungal activity, was synthesized in a longest linear sequence of 35 steps and 0.6 % overall yield. The synthetic approach is adaptable to the synthesis of congeners and analogues, as exemplified by the ready synthesis of ds-echinoside A and echinoside B, and thus will facilitate in-depth studies on the promising biological effects of echinoside A. Moreover, the present synthesis demonstrates the feasibility of synthetic access to the characteristic complex triterpene glycosides that occur ubiquitously in sea cucumbers.
Compound and applications of compound in treatment of cataract
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Paragraph 0117-0120, (2017/11/18)
The present invention discloses a compound and applications of the compound in treatment of cataract, wherein the structural formula of the compound is represented by a formula I, the compound represented by the formula I and the prodrug or pharmaceutically acceptable salt thereof can be used for preventing, alleviating, or reversing the aggregation of crystallin in cells, more than 90% of the protein components are crystallin (CRY) in the lens cell, and comprise alpha-CRY family, beta-CRY family and gamma-CRY family, and after the crystallin is subjected to mutation, the intracellular protein aggregation can be caused so as to cause the cataract disease. According to the present invention, the effect of the compound is detected by selecting the alpha-CRY family mutants such as alpha-Y118D and alphaB-R120 G, the beta-CRY family mutant such as betaB2-V187E, and the gamma-CRY family mutants such as gammaC-G129C and gammaD-W43R as the research model of the cataract disease; and compared to the existing small molecule (such as C29, Science, 350, 674), the small molecule having the novel structure of the present invention has good activity in the inhibition of the intraocular lens protein mutation induced protein aggregation, can improve the absorption of body on the drug, and does not have toxic-side effect on the normal lens cells.
Commands and method of treating cancer via RHO pathway
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Paragraph 0043, (2016/02/03)
Lanosterol derivatives useful as anti-cancer agent, which can inhibit the growth of lung cancer cells, liver cancer cells, mammary cancer cells, brain cancer cells and pancreatic cancer cells, possibly by acting on the RHO pathway. These lanosterol derivatives are represented by compound LD030:
Approach for expanding triterpenoid complexity via divergent Norrish-Yang photocyclization
Ignatenko, Vasily A.,Tochtrop, Gregory P.
, p. 3821 - 3831 (2013/06/26)
Triterpenoids comprise a very diverse family of polycyclic molecules that is well-known to possess a myriad of medicinal properties. Therefore, triterpenoids constitute an attractive target for medicinal chemistry and diversity-oriented synthesis. Photochemical transformations provide a promising tool for the rapid, green, and inexpensive generation of skeletal diversity in the construction of natural product-like libraries. With this in mind, we have developed a diversity-oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol are converted to the pseudosymmetrical polyketones by sequential allylic oxidation and oxidative cleavage of the bridging double bond at the B/C ring fusion. The resultant polyketones were hypothesized to undergo divergent Norrish-Yang cyclization to produce unique 6/4/8-fused triterpenoid analogues. The subtle differences between parent triterpenoids led to dramatically different spatial arrangements of reactive functionalities. This finding was rationalized through conformational analysis to explain unanticipated photoinduced pinacolization, as well as the regio- and stereochemical outcome of the desired Norrish-Yang cyclization.
Sterol C24-methyltransferase: Physio- and stereo-chemical features of the sterol C3 group required for catalytic competence
Howard, Alicia L.,Liu, Jialin,Elmegeed, Gamal A.,Collins, Emily K.,Ganatra, Kalgi S.,Nwogwugwu, Chizaram A.,Nes, W. David
body text, p. 43 - 50 (2012/08/07)
Sterol C24-methyltransferases (24-SMTs) catalyze the electrophilic alkylation of Δ24-sterols to a variety of sterol side chain constructions, and the C3- moiety is the primary determinant for substrate binding by these enzymes. To determine what specific structural features of the C3-polar group ensure sterol catalysis, a series of structurally related C3-analogs of lanosterol that differed in stereochemistry, bulk and electronic properties were examined against the fungal 24-SMT from Paracoccidioides brasiliensis (Pb) which recognize lanosterol as the natural substrate. Analysis of the magnitude of sterol C24-methylation activity (based on the kinetic constants of Vmax/Km and product distributions determined by GC-MS) resulting from changes at the C3-position in which the 3β-OH was replaced by 3α-OH, 3β-acetyl, 3-oxo, 3-OMe, 3β-F, 3β-NH2 (protonated species) or 3H group revealed that lanosterol and five substrate analogs were catalyzed and yielded identical side chain products whereas neither the 3H- or 3α-OH lanosterol derivatives were productively bound. Taken together, our results demonstrate a chemical complementarity involving hydrogen bonding formation of specific active site contacts to the nucleophilic C3-group of sterol is required for proper orientation of the substrate C-methyl intermediate in the activated complex.
Studies on the constituents of yellow cuban propolis: GC-MS determination of triterpenoids and flavonoids
Marquez Hernandez, Ingrid,Cuesta-Rubio, Osmany,Campo Fernandez, Mercedes,Rosado Perez, Aristides,Montes De Oca Porto, Rodny,Piccinelli, Anna Lisa,Rastrelli, Luca
experimental part, p. 4725 - 4730 (2011/07/09)
In this study, on the basis of the information supplied by NMR and HPLC-PDA data, we reported a quali-quantitative GC-MS study of 19 yellow Cuban propolis (YCP) samples collected in different regions of Cuba. The profiles of YCP samples allowed us to define two main types of YCP directly related to their secondary metabolite classes: type A, rich in triterpenic alcohols and with the presence of polymethoxylated flavonoids as minor constituents, and type B, containing acetyl triterpenes as the main constituents. For the first time, triterpenoids belonging to oleanane, lupane, ursane, and lanostane skeletons were reported as major compounds in propolis. Also, the presence of polymethoxylated flavones or flavanones was found for the first time in propolis.
Oxyfunctionalization of unactivated C-H bonds in triterpenoids with tert-butylhydroperoxide catalyzed by meso-5,10,15,20-tetramesitylporphyrinate osmium(II) carbonyl complex
Ogawa, Shoujiro,Wakatsuki, Yasuo,Makino, Mitsuko,Fujimoto, Yasuo,Yasukawa, Ken,Kikuchi, Takashi,Ukiya, Motohiko,Akihisa, Toshihiro,Iida, Takashi
experimental part, p. 165 - 171 (2010/06/19)
A system consisting of meso-5,10,15,20-tetramesitylporphyrinate osmium(II) carbonyl complex [Os(TMP)CO] as a precatalyst and tert-butylhydroperoxide (TBHP) as an oxygen donor is shown to be an efficient, regioselective oxidant system for the allylic oxidation, ketonization and hydroxylation of unactivated C-H bonds in a series of the peracetate derivatives of penta- and tetracyclic triterpenoids. Treatment of the substrates with this oxidant system afforded a variety of novel or scarce oxygenated derivatives in one-step. Structures of the isolated components, after chromatographic separation, were determined by spectroscopic methods including GC-MS and shift-correlated 2D-NMR techniques. Factors governing the regioselectivity and the possible mechanism for the oxyfunctionalization of the unactivated carbons are also discussed.
