Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins

Yang, Gangqiang; Gao, Meng; Sun, Yixiao; Wang, Conghui; Fang, Xiaojuan; Gao, Hongyan; Diao, Wenshuang; Yu, Hui

doi:10.1016/j.ejmech.2020.112507

Cited by 27 publications

(22 citation statements)

References 42 publications

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“…The antioxidant activity by DPPH radical scavenging method of all the compounds increased with an increase in concentration while compounds 67a and 67b showed 89.16% and 90.17% inhibition as compared to standard ascorbic acid (70.57%). Some new 3-amino acid derivatives of ocotillol-type sapogenins (Scheme 63) were designed and synthesized by Yang et al [103] as in vitro anti-inflammatory agents. All the compounds were subjected to a Griess assay to determine their ability to suppress LPS-induced NO production in RAW 264.7 macrophages.…”

Section: In Vitro Antiarthritic Agents Developed So Farmentioning

confidence: 99%

Therapeutic management of arthritis: A review on structural and target‐based approaches

Mahore

Kamboj

Kaleem

et al. 2022

Archiv der Pharmazie

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Inflammation is the natural defense mechanism against any external stimuli in the human body and it saves us from foreign entities that may alter our bodies' normal functioning. Any anomaly in this natural defense system leads to the development of different pathological conditions associated with chronic inflammation like rheumatoid arthritis, osteoarthritis, atopy, asthma, allergic rhino-conjunctivitis, coronary artery disease, cardiac arrhythmias, obesity, insulin resistance and type-2 diabetes, depression, and aging. These disorders impair the quality of life of affected people in different ways. Among these, rheumatoid arthritis and osteoarthritis are the most common chronic inflammation-associated disorders. Different therapeutic strategies are already available for the treatment of rheumatoid arthritis and osteoarthritis, but all with pros and cons. Here, we discuss the emergence of several antiarthritic analogs developed by different researchers which could provide the basis for the evolution of newer therapeutic strategies with better activity and safety profiles.

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Section: In Vitro Antiarthritic Agents Developed So Farmentioning

confidence: 99%

Therapeutic management of arthritis: A review on structural and target‐based approaches

Mahore

Kamboj

Kaleem

et al. 2022

Archiv der Pharmazie

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“…To obtain ginsenoside derivatives with better biological activity, a great deal of research has been made to structurally modify ginsenosides from the perspective of chemistry and pharmacology. 27,28) Among the structural modifications of PDQ, many amino acid derivatives had been designed and synthesized. For example, the amino acid derivatives of ginsenoside AD1 have anti-liver fibrosis activity, 29,30) and those of Pyxinol have P-glycoprotein (PGP)-mediated multiple drug resistance (MDR) activity.…”

Section: Introductionmentioning

confidence: 99%

Pseudo-sapogenin DQ 3-Maleate Derivative Induces Ovarian Carcinoma Cell Apoptosis <i>via</i> Mitochondrial Pathway

Han

Liu

Yang

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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In the present study, four novel ginsenosides fatty acid and aromatic acid derivatives were designed and synthesized, and their cytotoxic effects on human ovarian carcinoma cells (SKOV3) were assessed using the 3-( 4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that all derivatives inhibited SKOV3 cell growth, and Compound 3 showed the most outstanding antiproliferative effect on SKOV3 cells. The IC 50 value of Compound 3 was 33.8 2.21 µM, less than half of that of cis-platinum (70.1 7.64 µM). Subsequent analysis revealed that Compound 3 could promote SKOV3 cell apoptosis, and the percentage of apoptotic cell population increased with increasing Compound 3 concentrations. In addition, the expression ratios of Bax/Bcl-2, cleaved-Caspase-3/Caspase-3 and cleaved-Caspase-9/ Caspase-9 were gradually elevated in Compound 3-treated SKOV3 cells compared with control cells. Furthermore, translocation of Bax to mitochondria was associated with the release of Cytochrome C. Molecular docking analysis revealed three hydrogen-bonds existed in Compound 3 with poly(ADP-ribose)polymerase (PARP) receptor (PDB code: 5DSY), which may be the target of the anti-ovarian cancer effect of Compound 3. Altogether, our study indicates that Compound 3 induces SKOV3 cell apoptosis via reactive oxygen species (ROS)-dependent mitochondrial pathway, and can serve as an anti-cancer agent for treating ovarian carcinoma.

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“…Numerous scientific researchers devoted themselves to the modification or transformation of lead compounds with the purpose of obtaining derivative products with good properties [5][6][7][8]. Natural products and their structurally modified derivatives have been widely used as anti-tumor drugs due to the low toxicity and the ability of reversing multidrug resistance [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Ocotillol-type saponins or sapogenins, with a tetrahydrofuran ring in side chain, are the natural triterpenoids [13,14]. Pyxinol and ocotillol are two important sapogenins [11]. Pyxinol (CAS number: 25330-18-1) was isolated from some natural plants such as Pyxine endochrysina N YL , Notholaena rigidain, Salvia barrelieri and Betula humilis, respectively [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, pyxinol is also the active metabolite of protopanaxadiol (the main aglycon of ginsenosides) in human liver [19]. It was reported that pyxinol exhibited multiple pharmacological activities such as anti-cancer (including lung carcinoma, cervical carcinoma and colonic adenocarcinoma) [20][21][22], anti-multidrug resistance [11] and anti-inflammatory [23], etc. Ocotillol (CAS number: 5986-39-0)-firstly discovered from Panax pseudoginseng Subsp.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Anti-Hepatocarcinoma Effect of Amino Acid Derivatives of Pyxinol and Ocotillol

Zhang

et al. 2021

Molecules

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Aiming at seeking an effective anti-hepatocarcinoma drug with low toxicity, a total of 24 amino acid derivatives (20 new along with 4 known derivatives) of two active ocotillol-type sapogenins (pyxinol and ocotillol) were synthesized. Both in vitro and in vivo anti-hepatocarcinoma effects of derivatives were evaluated. At first, the HepG2 human cancer cell was employed to evaluate the anti-cancer activity. Most of the derivatives showed obvious enhanced activity compared with pyxinol or ocotillol. Among them, compound 2e displayed the most excellent activity with an IC50 value of 11.26 ± 0.43 µM. Next, H22 hepatoma-bearing mice were used to further evaluate the anti-liver cancer activity of compound 2e. It was revealed that the growth of H22 transplanted tumor was significantly inhibited when treated with compound 2e or compound 2e combined with cyclophosphamide (CTX) (p < 0.05, p < 0.01), and the inhibition rates of tumor growth were 35.32% and 55.30%, respectively. More importantly, compound 2e caused limited damage to liver and kidney in contrast with CTX causing significant toxicity. Finally, the latent mechanism of compound 2e was explored by serum and liver metabolomics based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. A total of 21 potential metabolites involved in 8 pathways were identified. These results suggest that compound 2e is a promising agent for anti-hepato-carcinoma, and that it also could be used in combination with CTX to increase efficiency and to reduce toxicity.

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Design, synthesis and anti-inflammatory activity of 3-amino acid derivatives of ocotillol-type sapogenins

Cited by 27 publications

References 42 publications

Therapeutic management of arthritis: A review on structural and target‐based approaches

Therapeutic management of arthritis: A review on structural and target‐based approaches

Pseudo-sapogenin DQ 3-Maleate Derivative Induces Ovarian Carcinoma Cell Apoptosis <i>via</i> Mitochondrial Pathway

Synthesis and Anti-Hepatocarcinoma Effect of Amino Acid Derivatives of Pyxinol and Ocotillol

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