842143-38-8Relevant articles and documents
Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
, p. 1954 - 1966 (2021/07/20)
Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
Synthesis of celastrol derivatives as potential non-nucleoside hepatitis B virus inhibitors
Zhang, He,Lu, Gongxi
, p. 1380 - 1386 (2020/07/13)
A series of para-quinone methide (pQM) moiety and C-20- modified derivatives of celastrol were synthesized and evaluated for their inhibitory effect on the secretion of HBsAg and HBeAg as well as the inhibitory effect against HBV DNA replication. The results suggested that amidation of C-20 carboxylic group could generate derivatives with good anti-HBV profile, among them compound 14 showed the best inhibitory activity on the secretion of HBsAg (IC50?=?11.9?μμ) and HBeAg (IC50?=?13.1?μμ) with SI of 3.3 and 3.0, respectively. In addition, 14 also showed potent inhibitory effect against HBV DNA replication (48.5?±?15.1%, 25?μM). This is, to our knowledge, the first report of celastrol derivatives as potential non-nucleoside HBV inhibitors.
Tripterine derivative, and preparation method and use thereof
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Paragraph 0075; 0076; 0080, (2017/01/17)
The invention discloses a tripterine derivative, and a preparation method and a use thereof. The tripterine derivative has a structure represented by formula I; and in the formula I, R1 is H, an alkyl group, a halogenated alkyl group, an unsaturated alkyl group, a hetero atom-containing alkyl group or an aryl group, R2 is an alkyl group, a halogen, an alkyloxy group or a nitro group, and R3 is H or an alkyl group. In the preparation method of the tripterine derivative, an indolyl group or a substituted indolyl group is introduced to the 6 position of tripterine through a Friedel-Crafts reaction under mild reaction conditions. The tripterine derivative has the characteristics of high anticancer activity, low toxicity, small side effects and stable structure in the treatment of cancers.
