1258-84-0Relevant articles and documents
Synthesis of celastrol derivatives as potential non-nucleoside hepatitis B virus inhibitors
Zhang, He,Lu, Gongxi
, p. 1380 - 1386 (2020)
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.
SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway
Chen, Ziwen,Zhang, Duo,Yan, Siwei,Hu, Chaochao,Huang, Zhenfei,Li, Zhuoer,Peng, Shuangzhou,Li, Xiaotong,Zhu, Yi,Yu, Hongyu,Lian, Baohuan,Kang, Qi,Li, Mingyu,Zeng, Zhiping,Zhang, Xiao-Kun,Su, Ying
, p. 171 - 187 (2019)
Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent
Scaffold hopping of celastrol provides derivatives containing pepper ring, pyrazine and oxazole substructures as potent autophagy inducers against breast cancer cell line MCF-7
Feng, Yao,Fu, Xuefeng,Li, Zhaolin,Lin, Fengwei,Lv, Jialun,Mao, Qing,Mou, Yanhua,Wang, Shaojie,Yang, Yajun,Zhang, Bing,Zhang, Lei,Zhang, Peng,Zhao, Jiaxing
, (2022/03/16)
Three series of celastrol derivatives, namely, 6a–6i, 11a–11i and 15a–15i, were designed based on the scaffold hopping strategy. The derivatives were synthesized and biologically evaluated against five human tumor cell lines (i.e. A549, MCF-7, Bel7402, HT-29 and PC3) using MTT assay in vitro. Results showed that compound 11i exhibited apparent antiproliferative activity against the MCF-7 cell line with an IC50 value of 1.31 μM and could remarkably inhibit the colony formation of the MCF-7 cells. Transmission electron microscopy assay, monodansylcadaverine incorporation assay and the expression of LC3 A/B, p62 and Beclin-1 in MCF-7 cells suggested that the potent antiproliferative activity of compound 11i was mainly due to its autophagy-inducing effect. Moreover, compound 11i could arrest the MCF-7 cells in the G2/M phase by regulating the cell-cycle-related proteins Cdk-1 and Cyclin B1. In the zebrafish xenograft model, compound 11i could obviously inhibit the proliferation of the MCF-7 cells. Thus, compound 11i could serve as a promising lead compound for breast cancer therapy.
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.
Tripterine derivative and preparation method and application thereof
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Paragraph 0025; 0051-0052, (2021/07/24)
The invention discloses a tripterine derivative and a preparation method and application thereof, and belongs to the technical field of medicines. The invention aims to provide a tripterine derivative with low toxicity and antitumor activity and a prepara