Synthesis of celastrol derivatives as potential non‐nucleoside hepatitis B virus inhibitors

Zhang, He; Lu, Gongxi

doi:10.1111/cbdd.13746

Cited by 4 publications

(1 citation statement)

References 53 publications

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“…As previously reported for other methylene quinones and phenolic nor-triterpenes compounds, replacement of the carboxylic group present in celastrol on C-29 by a methyl ester group reduces the antibacterial activity [14,43]. Celastrol has shown interesting pharmacological activities, although inconveniences related to poor water solubility, high toxicity, or poor stability have also been described [29,44]. Structural modifications in the triterpene quinones scaffolds could be of interest to obtain derivatives with improved antimicrobial activities and to overcome the pharmacokinetic limitations of these compounds.…”

Section: Antimicrobial Activitymentioning

confidence: 80%

Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources

Padilla-Montaño

Guerra

Moujir

2021

Foods

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Species of the Celastraceae family are traditionally consumed in different world regions for their stimulating properties. Celastrol, a triterpene methylene quinone isolated from plants of celastraceas, specifically activates satiety centers in the brain that play an important role in controlling body weight. In this work, the antimicrobial activity and mechanism of action of celastrol and a natural derivative, pristimerin, were investigated in Bacillus subtilis. Celastrol showed a higher antimicrobial activity compared with pristimerin, being active against Gram-positive bacteria with minimum inhibitory concentrations (MICs) that ranged between 0.16 and 2.5 µg/mL. Killing curves displayed a bactericidal effect that was dependent on the inoculum size. Monitoring of macromolecular synthesis in bacterial populations treated with these compounds revealed inhibition in the incorporation of all radiolabeled precursors, but not simultaneously. Celastrol at 3 µg/mL and pristimerin at 10 µg/mL affected DNA and RNA synthesis first, followed by protein synthesis, although the inhibitory action on the uptake of radiolabeled precursors was more dramatic with celastrol. This compound also caused cytoplasmic membrane disruption observed by potassium leakage and formation of mesosome-like structures. The inhibition of oxygen consumption of whole and disrupted cells after treatments with both quinones indicates damage in the cellular structure, suggesting the cytoplasmic membrane as a potential target. These findings indicate that celastrol could be considered as an interesting alternative to control outbreaks caused by spore-forming bacteria.

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