One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities

Sun, Yulong; Liu, Jia; Jiang, Xianxing; Sun, Tao; Liu, Luping; Zhang, Xiaoyuan; Ding, Shaoli; Li, Jingyi; Zhuang, Yan; Wang, Yiqing; Wang, Rui

doi:10.1038/srep13699

Cited by 32 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, drug development has often relied on the use of natural and synthetic drugs for the prevention or treatment of many diseases [ 8 ]. Compared with synthetic drugs, natural anti-inflammatory ingredients attract more and more attention due to their weak side effects [ 1 , 9 ]. Currently, many natural ingredients have been put into clinical use as anti-inflammatory drugs, such as triptolide, resveratrol, silymarin [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

Wang

Guan

Yang

et al. 2020

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Inflammation is a response to tissue injuries, which is indispensable and important for human health, but excessive inflammation can potentially cause damage to the host organisms. Camellia nitidissima Chi, one traditional medicinal and edible plant in China, was reported to exhibit anti-inflammation capability. Hence, this study was conducted to isolate the bioactive compounds from the flowers of C. nitidissima Chi and evaluate their anti-inflammatory activity. Methods The phytochemicals from the flowers of C. nitidissima Chi were isolated and purified by silica gel, Sephadex LH-20 gel, C18 reversed silica gel, semi-preparative HPLC, and identified by the spectrum technologies. The anti-inflammatory activity of isolated compounds was evaluated using cultured macrophage RAW 264.7 cells. Whereafter the potential metabolic mechanism of the anti-inflammatory activity of the bioactive compound was investigated by a 1H-NMR based metabolomics approach. The metabolites in 1H-NMR spectra were identified by querying the Human Metabolome Database and Madison Metabolomics Consortium Database online. And the multivariate statistical analysis was performed to evaluate the variability of metabolites among samples and between sample classes. Results The compound isolated from the flowers of C. nitidissima Chi was identified as 3-cinnamoyltribuloside (3-CT). 3-CT could inhibit the NO production and the mRNA expression of iNOS involved in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Moreover, 3-CT could inhibit the expression of a series of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, both at the mRNA level and protein level. The 1H-NMR based metabolomics approach was applied to investigate the potential metabolic mechanism of the anti-inflammatory activity of 3-CT. Thirty-five metabolites were identified and assigned. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the 1H-NMR data showed 3-CT could balance the significant changes in many endogenous metabolites (e.g., choline, glucose, phenylalanine) induced by LPS in RAW 264.7 cells, which related to cholinergic anti-inflammatory pathway, oxidative stress, energy metabolism, and amino acids metabolism. Conclusion 3-CT, isolated from the flowers of C. nitidissima Chi, had potent anti-inflammatory activity in LPS-activated RAW 264.7 cells. Furthermore, our results indicated that 3-CT had effects on the cholinergic anti-inflammatory pathway, oxidative stress, energy metabolism, and amino acids metabolism in LPS-activated RAW 264.7 cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

Wang

Guan

Yang

et al. 2020

BMC Complement Med Ther

View full text Add to dashboard Cite

show abstract

“…Anticancer drugs are required with novel structural features to overcome multidrug resistance and severe side-effects and to enhance the effectiveness of cancer treatment (29,30). Oxindole derivatives are specialized structures and exerted various biological activities, ranging from MDM2 antagonists (31,32), ion channel blockers (33) and anti-inflammatory agents (34,35) to various protein kinase inhibitors. A number of indole-based compounds inhibit various protein kinase families such as receptor tyrosine kinases (RTKs) and serine/ threonine-specific protein kinases (5,10,36,37).…”

Section: Discussionmentioning

confidence: 99%

An β-quaternary chiral latam derivative, YH-304 as a novel broad-spectrum anticancer agent

Hwang

Park

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Previously, we reported that α-quaternary chiral lactam derivatives have broad spectrum anticancer activity. However, the underlying molecular mechanisms and its relevance are largely unknown. In the present study, we report progress on α-quaternary chiral lactam analogues that address this, focusing on the novel analogue YH-304 as a candidate to broadly target human cancer cells. The effect of YH-304 on cell transformation was assessed by clonogenic assay in non-small cell lung cancer cells (NSCLCs) A549 and 226B. Proapoptotic activity of YH-304 was determined by TUNEL assay and cleaved PARP, cleaved caspase-9, and Bax as markers for apoptosis. The p53-dependency and therapeutic spectrum of YH-304 was assessed by western blot analysis, real-time PCR, and cell viability assays in cells expressing endogenous wild or mutant p53. The effect of YH-304 on angiogenesis in vivo was examined by bFGF-mediated angiogenesis assay in zebrafish. Finally, the effect of YH-304 on AKT and ERK activation (phosphorylation) as a putative mechanism underlying the effect of YH-304 on bFGF-mediated angiogenesis was assessed using western blotting. We found that YH-304 significantly decreases the colony-forming activities of both A549 and 226B cells, inducing cellular apoptosis. Unlike nutlin-3 (p53 pathway activator), YH-304 did not affect the expression levels of p53 and its target gene such as p21 and thus showed p53-independent anticancer activity with broad spectrum. In addition, YH-304 inhibited bFGF-induced angiogenesis in vivo through mediating AKT and ERK signaling pathway, which plays an important role in bFGF activation and angiogenesis. Taken together, our data indicate that YH-304 may represent a novel therapeutic option for the treatment of cancer in a p53-independent manner.

show abstract

“…Nitrogen and oxygen containing spirooxindoles are a privileged class of compounds having great relevance in biological and medicinal fields such as vasodilators, [6] antitumor, [7] antidiabetic, [8] antipyretic, [9] and analgesic, [10] etc. Due to their extensive importance in biological system, various methodologies have been developed for their synthesis.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐Assisted Synthesis of Nitrogen and Oxygen Containing Heterocycles Using Fluorinated Graphene Oxide as Catalyst: Evaluation of Their Anthelmintic Activities

et al. 2020

View full text Add to dashboard Cite

Spirooxindole derivatives have been efficiently synthesized via a three-component reaction consisting of isatin, malononitrile/ pyrazole and various 1,3-diketones using Fluorinated Graphene Oxide (FGO) as a green and metal free carbocatalyst, under sonication. The main advantages of this synthetic approach lie in its operational simplicity, easy catalyst recovery and recyclability, high yields and short reaction times. The prepared catalyst was characterized by various analytical techniques viz., UV-Vis, FT-IR Spectroscopy, TGA, TEM, FE-SEM and EDX. The in vitro anthelmintic screening of synthesized compounds against a cestode, Raillietina sp. and a nematode parasite, Syphacia obvelata at 200 μg/mL and 800 μg/mL were also carried out which revealed a profound activity, with much reduced morality time of parasite. The SEM study indicated structure alterations in treated parasite, further validating the in vitro anthelmintic property. In addition, molecular docking studies were carried out against β-tubulin protein to determine binding affinity of the synthesized compounds. All test compound followed the "Lipinski Rule of Five" and in silico pharmacokinetic investigation showed inhibitory activity against CYP enzyme and P-glycoprotein which may further improve the bio efficacy of compounds.

show abstract

One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities

Cited by 32 publications

References 16 publications

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

Anti-inflammatory activity of 3-cinnamoyltribuloside and its metabolomic analysis in LPS-activated RAW 264.7 cells

An β-quaternary chiral latam derivative, YH-304 as a novel broad-spectrum anticancer agent

Ultrasound‐Assisted Synthesis of Nitrogen and Oxygen Containing Heterocycles Using Fluorinated Graphene Oxide as Catalyst: Evaluation of Their Anthelmintic Activities

Contact Info

Product

Resources

About