Synthesis and biological evaluation of suffrutines A, B and their N-fused analogues

Zhu, Zefeng; Chen, Chun; Jiang, Jingxing; Zhang, Qianzhong; Du, Z.; Wei, Shuxian; Song, Xianheng; Tang, Jie; Lei, Jinping; Ke, Zhuofeng; Zou, Yong

doi:10.1039/d0qo00050g

Cited by 2 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SA and SB are novel components with E,E and Z,E isomeric indolizidine alkaloids extracted from the roots of F. suffruticosa. Previous studies regarding the biological activity of SA and SB mainly focused on the effects such as inducing the differentiation of Neuro-2a cells and inhibiting proliferation of tumor cells [20,22]; none of these studies were devoted to evaluating the effects of SA and SB on inflammation responses. Thus, the aim of this study was to explore and compared the effects and mechanisms of SA and SB on inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

“…The natural products SA and SB, with ≥ 98 % purity, were previously synthesized in our group. Their structures were elucidated by a series of NMR spectra and single-crystal X-ray crystallography [22]. These compounds were dissolved respectively in DMSO and kept at − 20°C in dark conditions.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…Moreover, as the SA and SB are a pair of E,E and Z,E isomers, the difference of the isomeric structure would probably result in a difference in biological activity. For example, preliminary studies demonstrated that SA could induce the differentia-tion of Neuro-2a cells and exhibit antiproliferative activity in tumor cells, whereas SB did not show comparable effects [20,22]. Further pharmacological activities and underlying mechanisms regarding SA and SB have not been reported thus far.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

Flueggea suffruticosa is a traditional Chinese medicine that has been commonly used for the treatment of inflammatory ailments, including rheumatism and lumbago. Suffrutines A and suffrutines B are a pair of novel E,E and Z,E isomeric indolizidine alkaloids isolated from the roots of F. suffruticosa. However, their anti-inflammatory activity has not been reported thus far. The aim of this study was to investigate the inhibitory effect of inflammatory mediators and possible mechanisms of suffrutines A and B in lipopolysaccharide-induced RAW264.7 cells. Results showed that suffrutines A and B could remarkably inhibit the production of nitric oxide, prostaglandin E2, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in lipopolysaccharide-induced RAW264.7 cells. Further evaluation demonstrated that compared with suffrutines A, suffrutines B could more significantly inhibit the phosphorylation of IKKα/β, the degradation of IκBα, and the nuclear translocation of the p65 and p52 subunits in the canonical and non-canonical nuclear factor-κB pathways. Therefore, suffrutines B exhibited more potent inhibitory activity on inflammatory mediators than suffrutines A.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Chemicals and Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The developments of apoptosis inducers have become effective methods for cancer therapy. [5,6] In general, there is a balance between apoptosis and proliferation in normal cells. [7] The balance depends on the Bcl-2/Bax ratio.…”

mentioning

confidence: 99%

Synthesis and antitumor potential of new arylidene ursolic acid derivatives via caspase‐8 activation

Zhu

Chen

et al. 2021

Archiv der Pharmazie

View full text Add to dashboard Cite

Continuing our studies on NO-donating ursolic acid-benzylidene derivatives as potential antitumor agents, we designed and synthesized a series of new arylidene derivatives containing NO-donating ursolic acid and aromatic heterocyclic units.Compounds 5c and 6c showed a significant broad-spectrum antitumor activity.Compound 5c exhibited nearly three-to nine-fold higher cytotoxicity as compared with the parent drug in A549, MCF-7, HepG-2, HT-29, and HeLa cells, and it was also found to be the most potent apoptosis inducer of MCF-7 cells. More importantly, compound 5c arrested the MCF-7 cell cycle in the G1 phase, which was associated with caspase activation and a decrease of the Bcl-2/Bax ratio. Meanwhile, compound 5c caused changes in morphological features, dissipation of the mitochondrial membrane potential, and accumulation of reactive oxygen species. A docking study revealed that the nitroxyethyl moiety of compound 5c may form hydrogen bonds with caspase-8 amino acid residues (SER256 and HIS255). Together, these data suggest that NO-donating ursolic acid-arylidene derivatives are potent apoptosis inducers in tumor cells.antitumor activity, apoptosis inducer, NO donor prodrug, ursolic acid derivatives | INTRODUCTIONApoptosis (also called programmed cell death) was described to perform various functions in development. [1] It plays an important role not only in embryogenesis but also in the regulation of cell numbers and the elimination of unwanted cells. The previous literature pointed out that irregularity in apoptosis may cause a number of human diseases, such as neurodegenerative disorders, immunodeficiency, AIDS, and cancer. [2][3][4] Subsequent studies confirmed that apoptosis is one of the major pathways involved in the proliferation, migration, and invasion of tumor cells. Most of the cytotoxic compounds were reported to induce apoptosis in cancer cells. The developments of apoptosis inducers have become effective methods for cancer therapy. [5,6] In general, there is a balance between apoptosis and proliferation in normal cells. [7] The balance depends on the Bcl-2/Bax ratio. It is worth noting that high levels of Bcl-2/Bax ratio may increase the risk of cancer. An excess of Bcl-2 promotes migration and invasion of tumor cells. [8] Morphological alterations, including cell shrinkage, chromatin condensation, and nuclear fragmentation, are important features of tumor cell apoptosis. [9] It has been proved that most of the morphological changes are caused by caspase family proteases. Caspases are divided into three subfamilies, I (caspase-2, -8, -9, and -10),

show abstract

Synthesis and biological evaluation of suffrutines A, B and their N-fused analogues

Abstract: The synthesis, structure confirmation, stability and isomerization features of suffrutines A, B and their N-fused analogues were reported. Biological tests showed that the introduction of nitrogen atom might be beneficial to the anticancer activity.

Cited by 2 publications

References 54 publications

Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

Synthesis and antitumor potential of new arylidene ursolic acid derivatives via caspase‐8 activation

Contact Info

Product

Resources

About