Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Pang, Chaohai; Luo, Jinhui; Liu, Chunhua; Wu, Xuejin; Wang, Dingyong

doi:10.1002/cbdv.201800059

Cited by 15 publications

(16 citation statements)

References 41 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compounds 146 and 150 showed potent antiproliferation effects. Moreover, Compound 150 showed 10‐fold stronger effect than celastrol in A549 cells, with an IC 50 value of 0.109 µm 90 . In another study, the researchers found that celastrol conjugated with glucosamine is more secure than celastrol in acute renal injury treatment 91 .…”

Section: Chemical Synthesis and Structural Modificationsmentioning

confidence: 98%

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Lü

Liu

Zhou

et al. 2020

Medicinal Research Reviews

View full text Add to dashboard Cite

Celastrol, a quinone‐methide triterpenoid, was extracted from Tripterygium wilfordii Hook. F. in 1936 for the first time. Almost 70 years later, it is considered one of the molecules most likely to be developed into modern drugs, as it exhibits notable bioactivity, including anticancer and anti‐inflammatory activity, and exerts antiobesity effects. In addition, the molecular mechanisms underlying its bioactivity are being widely studied, which offers new avenues for its development as a pharmaceutical reagent. Owing to its potential therapeutic effects and unique chemical structure, celastrol has attracted considerable interest in the fields of organic, biosynthesis, and medicinal chemistry. As several steps in the biosynthesis of celastrol have been revealed, the mechanisms of key enzymes catalyzing the formation and postmodifications of the celastrol scaffold have been gradually elucidated, which lays a good foundation for the future heterogeneous biosynthesis of celastrol. Chemical synthesis is also an effective approach to obtain celastrol. The total synthesis of celastrol was realized for the first time in 2015, which established a new strategy to obtain celastroid natural products. However, owing to the toxic effects and suboptimal pharmacological properties of celastrol, its clinical applications remain limited. To search for drug‐like derivatives, several structurally modified compounds were synthesized and tested. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of celastrol. We anticipate that this paper will facilitate a more comprehensive understanding of this promising compound and provide constructive references for future research in this field.

show abstract

Section: Chemical Synthesis and Structural Modificationsmentioning

confidence: 98%

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Lü

Liu

Zhou

et al. 2020

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Besides, compounds (6) and (7) have a strong antiproliferative activity of Hela and A549 cell lines, which are 5 and 10 times that of celastrol (Zhang H.-J. et al, 2018;Pang et al, 2018;Wang G. et al, 2019). On the other hand, the water solubility of compound (8) is 35 times that of celastrol and its tumor suppressive activity is higher than celastrol against the PANC-1 cell line and the human lung cancer (paclitaxelresistant) A549 cell line (Jiang et al, 2016).…”

Section: Increase Solubility To Enhance Antitumor Effectsmentioning

confidence: 99%

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Shi

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Celastrol, a natural bioactive ingredient derived from Tripterygium wilfordii Hook F, exhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc. However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application. To address this issue, some strategies were employed to improve the anticancer efficacy and reduce the side-effects of celastrol. The present review comprehensively focuses on the various challenges associated with the anticancer efficiency and drug delivery of celastrol, and the useful approaches including combination therapy, structural derivatives and nano/micro-systems development. The specific advantages for the use of celastrol mediated by these strategies are presented. Moreover, the challenges and future research directions are also discussed. Based on this review, it would provide a reference to develop a natural anticancer compound for cancer treatment.

show abstract

“…In the series of amino acid derivatives, compound 99 showed the highest anticancer activity against AGS cell lines (IC 50 = 0.44 μM) and showed better anticancer activity against HCT-116, BEL-7402, and HepG-2 cell lines than the other compounds. Eight novel celastrol amino acid derivatives were synthesized, which displayed strong cytotoxic activities against A549, HeLa, and HepG-2 cell lines (Pang et al, 2018 ). In particular, the cytotoxicities of 100 and 101 against HeLa and A549 cells with IC 50 values ranging from 0.109 to 0.371 μM, the effect of cytotoxic activity was remarkably stronger than that of celastrol and cisplatin.…”

Section: Application Of Amino Acids In the Structural Modification Of Natural Productsmentioning

confidence: 99%

Application of Amino Acids in the Structural Modification of Natural Products: A Review

Deng

et al. 2021

Front. Chem.

View full text Add to dashboard Cite

Natural products and their derivatives are important sources for drug discovery; however, they usually have poor solubility and low activity and require structural modification. Amino acids are highly soluble in water and have a wide range of activities. The introduction of amino acids into natural products is expected to improve the performance of these products and minimize their adverse effects. Therefore, this review summarizes the application of amino acids in the structural modification of natural products and provides a theoretical basis for the structural modification of natural products in the future. The articles were divided into six types based on the backbone structures of the natural products, and the related applications of amino acids in the structural modification of natural products were discussed in detail.

show abstract

Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Cited by 15 publications

References 41 publications

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Application of Amino Acids in the Structural Modification of Natural Products: A Review

Contact Info

Product

Resources

About