- Cucurbitacin derivatives and preparation method thereof
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The invention discloses multiple new derivatives of cucurbitacin-B and cucurbitacin-E and salts of the new derivatives, and also discloses a preparation method of the new derivatives. As the new derivatives and the salts thereof have the same basic structures as cucurbitacin-B and cucurbitacin-E respectively, the nature of the new derivatives and the salts thereof is basically the same as that ofcucurbitacin-B and cucurbitacin-E, and the new derivatives and the salts thereof have good anti-cancer, anti-virus, anti-inflammation and liver protection effects with low toxic and side effects.
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Paragraph 0129
(2018/04/21)
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- Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery
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Heat shock protein 90 (Hsp90) facilitates the maturation of many newly synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in which Hsp90 forms a heteroprotein complex and relies upon cochaperones, immunophilins, etc., for assistance in client folding. Hsp90 inhibition has emerged as a strategy for anticancer therapies due to the involvement of clients in many oncogenic pathways. Inhibition of chaperone function results in client ubiquitinylation and degradation via the proteasome, ultimately leading to tumor digression. Small molecule inhibitors perturb ATPase activity at the N-terminus and include derivatives of the natural product geldanamycin. However, N-terminal inhibition also leads to induction of the pro-survival heat shock response (HSR), in which displacement of the Hsp90-bound transcription factor, heat shock factor-1, translocates to the nucleus and induces transcription of heat shock proteins, including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is an effective strategy to prevent client maturation without induction of the HSR. Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-isocucurbitacin D prevented client maturation without induction of the HSR. Cucurbitacin D also disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23.
- Hall, Jessica A.,Seedarala, Sahithi,Rice, Nichole,Kopel, Lucas,Halaweish, Fathi,Blagg, Brian S. J.
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p. 873 - 879
(2015/05/13)
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- Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells
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Cucurbitane-type triterpenes, cucurbitacins B and E, were reported to exhibit cytotoxic effects in several cell lines mediated by JAK/STAT3 signaling. However, neither compound inhibited phosphorylation of STAT3 in human leukemia (U937) cells at low concentrations. We therefore synthesized a biotin-linked cucurbitacin E to isolate target proteins based on affinity for the molecule. As a result, cofilin, which regulates the depolymerization of actin, was isolated and suggested to be a target. Cucurbitacins E and I inhibited the phosphorylation of cofilin in a concentration-dependent manner, and their effective concentrations having the same range as the concentrations at which they had cytotoxic effects in U937 cells. In addition, the fibrous-/globular-actin ratio was decreased after treatment with cucurbitacin E in HT1080 cells. These findings suggested that the inhibition of cofilin's phosphorylation increased the severing activity of cofilin, and then the depolymerization of actin was enhanced after treatment with cucurbitacin E at lower concentrations.
- Nakashima, Souichi,Matsuda, Hisashi,Kurume, Ai,Oda, Yoshimi,Nakamura, Seikou,Yamashita, Masayuki,Yoshikawa, Masayuki
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experimental part
p. 2994 - 2997
(2010/08/20)
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- CUCURBITACIN COMPOUNDS
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Cucurbitacins, cucurbitacin derivatives, and methods for making and using the same are provided.
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Page/Page column 7-8
(2008/06/13)
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