scholarly journals Design and Synthesis of C-19 Isosteviol Derivatives as Potent and Highly Selective Antiproliferative Agents

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 121 ◽  
Author(s):  
Tian Luan ◽  
Li-Hua Cao ◽  
Hao Deng ◽  
Qing-Kun Shen ◽  
Yu-Shun Tian ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Human Cancer ◽  
Parent Compound ◽  
Cyclin A ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cyclin E1 ◽  
Hct 116

Six series of novel isosteviol derivatives; modified in the C-19 position; were synthesized; and their antiproliferative activity was evaluated against three human cancer cell lines (HCT-116; BEL-7402; HepG2) and the human L02 normal cell line in vitro. Most of the derivatives tested here exhibited improved antiproliferative activity with high selectivity when compared with the parent compound isosteviol and the positive control drug 5-fluorouracil. Among these derivatives; compound 5d exhibited the most potent antiproliferative activity and commendable selectivity between cancer and normal cells. In addition; compound 5d inhibited the colony formation of HCT-116 cells in a concentration-dependent manner. Further studies revealed that compound 5d arrested the HCT-116 cell cycle in the S phase; and western blot analysis demonstrated the mechanism may be correlated with a change in the expression of cyclin A; cyclin B1; and cyclin E1. Furthermore; the results of a docking study that involved placing compound 5d into the CDK2/cyclin A binding site revealed that its mode of action was possibly as a CDK2/cyclin A inhibitor.

scholarly journals In vitro Cancer Cell Growth Inhibition and Antioxidant Activity of Bombax ceiba (Bombacaceae) Flower Extracts

2014 ◽  
Vol 9 (5) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Rosa Tundis ◽  
Khaled Rashed ◽  
Ataa Said ◽  
Francesco Menichini ◽  
Monica R. Loizzo
Keyword(s):  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Dependent Manner ◽  
Bleaching Test ◽  
Β Carotene

The flowers of Bombax ceiba were investigated for their chemical composition, antioxidant effects and antiproliferative activity against seven human cancer cell lines. The antiproliferative responses of diethyl ether (DE) and light petroleum (PE) extracts were evaluated by sulforhodamine B (SRB) assay against MCF-7, HeLa, COR-L23, C32, A375, ACHN, and LNCaP cells in comparison with a human normal cell line, 142BR. Moreover, extracts were characterized by GC-MS analysis and tested for their antioxidant properties by different in vitro systems, namely DPPH, Fe-chelating activity and β-carotene bleaching test. Both PE and DE extracts showed the highest antiproliferative activity against human renal adenocarcinoma (ACHN) in a concentration-dependent manner. PE extract showed the highest radical scavenging activity against the DPPH radical, while DE extract was more active in the β-carotene bleaching test. The presence of β-sitosterol and some fatty acids may contribute to the bioactivity of B. ceiba flower extracts.

scholarly journals (R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function

2014 ◽  
Vol 121 (1) ◽  
pp. 149-159 ◽  
Author(s):  
Rajib K. Paul ◽  
Nagendra S. Singh ◽  
Mohammed Khadeer ◽  
Ruin Moaddel ◽  
Mitesh Sanghvi ◽  
...  
Keyword(s):  
Parent Compound ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Dependent Manner ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Concentration Dependent Manner ◽  
Pheochromocytoma Cells ◽  
The Impact

Abstract Background: Subanesthetic doses of (R,S)-ketamine are used in the treatment of neuropathic pain and depression. In the rat, the antidepressant effects of (R,S)-ketamine are associated with increased activity and function of mammalian target of rapamycin (mTOR); however, (R,S)-ketamine is extensively metabolized and the contribution of its metabolites to increased mTOR signaling is unknown. Methods: Rats (n = 3 per time point) were given (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)-hydroxynorketamine and their effect on the mTOR pathway determined after 20, 30, and 60 min. PC-12 pheochromocytoma cells (n = 3 per experiment) were treated with escalating concentrations of each compound and the impact on the mTOR pathway was determined. Results: The phosphorylation of mTOR and its downstream targets was significantly increased in rat prefrontal cortex tissue by more than ~2.5-, ~25-, and ~2-fold, respectively, in response to a 60-min postadministration of (R,S)-ketamine, (R,S)-norketamine, and (2S,6S)-hydroxynorketamine (P < 0.05, ANOVA analysis). In PC-12 pheochromocytoma cells, the test compounds activated the mTOR pathway in a concentration-dependent manner, which resulted in a significantly higher expression of serine racemase with ~2-fold increases at 0.05 nM (2S,6S)-hydroxynorketamine, 10 nM (R,S)-norketamine, and 1,000 nM (R,S)-ketamine. The potency of the effect reflected antagonistic activity of the test compounds at the α7-nicotinic acetylcholine receptor. Conclusions: The data demonstrate that (R,S)-norketamine and (2S,6S)-hydroxynorketamine have potent pharmacological activity both in vitro and in vivo and contribute to the molecular effects produced by subanesthetic doses of (R,S)-ketamine. The results suggest that the determination of the mechanisms underlying the antidepressant and analgesic effects of (R,S)-ketamine requires a full study of the parent compound and its metabolites.

scholarly journals Lipophilised resveratrol affects the generation of reactive nitrogen species in murine macrophages and cell viability of human cancer cell lines

2019 ◽  
Vol 7 ◽  
Author(s):  
Won Young Oh ◽  
Yi-Shiou Chiou ◽  
Min-Hsiung Pan ◽  
Fereidoon Shahidi
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Human Cancer ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitrite Production ◽  
Anti Inflammatory ◽  
Ht 29

Resveratrol was esterified with selected fatty acids to improve its lipophilicity and potential application in food and biological systems. In this study, resveratrol and monoesters of resveratryl propionate (RC3:0) and resveratryl docosahexaenate (RDHA) were examined for their effects on anti-inflammatory and anti-proliferative activity in vitro.  All test compounds showed a decreased nitrite production in murine RAW 264.7 cells in a concentration dependent manner. Resveratrol, RC3:0, and RDHA were evaluated for their effects on cell viability using liver cancer (HepG2), colon cancer (HT-29, A431), breast cancer (MCF7), and gastric cancer (AGS) cell lines. All test compounds showed decreased cell viability of HepG2, A431, MCF7, HT-29, and AGS in a concentration-dependent manner. The results suggest that resveratrol esters may serve as potential anti-inflammatory and anti-proliferative agents.

Apoptosis Inducing Effects of Thymus linearis Methanolic Extract in HCT-116 Cells and LC-MS Chemical Profiling of Its Active Constituents

2021 ◽  
Vol 11 ◽  
Author(s):  
Rohina Bashir ◽  
Ovais Zargar ◽  
Qazi Parvaiz ◽  
Rabia Hamid
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Dna Cleavage ◽  
Methanolic Extract ◽  
Dependent Manner ◽  
Regulation Of Expression ◽  
Anti Cancer ◽  
Hct 116 ◽  
Hct 116 Cells

Background: Cancer is one of the major problems at present, to which vast research is being dedicated to find effective remedy. Medicinal plants are endowed with numerous molecules that could be effective in multiple diseases including cancer. Thymus linearis, being rich in phenols, terpenoid, and flavonoids have potential to provide anti-cancer entities. Methods: The extracts of Thymus linearis were investigated for in vitro anticancer activity using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on a panel of cancer cell lines. The cellular and nuclear morphology was studied using microscopic techniques. Agarose gel electrophoresis was used for DNA fragmentation analysis. Protein expression was determined by western-blotting. LC-MS was used for phytochemical identification. Results: Among all the extracts, Thymus linearis methanolic (TLM) extract was found to exhibit antiproliferative activity on cell lines to varied degrees. TLM was found to be most potent against HCT-116 with an IC50 of 158μg/ml after 48hrs treatment, while being nontoxic to HEK-293 and FR-2 cells under similar concentrations. TLM decreased clonogenic potential of HCT-116 cells. It induced cell shrinkage, membrane blebbing and nuclear fragmentation characteristic of apoptotic in a dose dependent manner in HCT-116 cells. Prominent internucleosomal DNA cleavage was observed in HCT-116 cells after 48hrs TLM treatment. Western blot analysis revealed the up regulation of expression of Bax, caspases 9 and caspases 3 and downregulation of Bcl-2 proteins. The LC-MS data revealed the presence of Salvianolic acid H, Synparvolide C, Thymuside A and Jasmonic acid; 12-Hydroxy, O-β-D-glucopyranoside and polyphenolic flavonoids to which antiproliferative activity can be attributed. Conclusion: The results suggest that Thymus linearis methanolic extract could be valuable source of anti-cancer agents.

scholarly journals Ginkgo biloba Exocarp Extract Inhibits the Metastasis of B16-F10 Melanoma Involving PI3K/Akt/NF-κB/MMP-9 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chenjie Cao ◽  
Ya Su ◽  
Yanqi Gao ◽  
Chengrong Luo ◽  
Lu Yin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ginkgo Biloba ◽  
Human Cancer ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Human Cancer Cells ◽  
Umbilical Vein Endothelial Cells

In recent years, interest in natural plant extracts for cancer treatment is growing in the drug development field. Ginkgo biloba exocarp extract (GBEE) is known for possessing inhibitory effects on various mouse and human cancer cells. And no adverse reactions were observed during its clinical application to cancer patients. The aim of this study is to investigate the inhibitory effect of GBEE on the metastasis of B16-F10 melanoma and its related mechanisms. The B16-F10 melanoma lung metastasis model was established in C57BL/6J mice. It was found that GBEE inhibited the growth and pulmonary metastasis of B16-F10 melanoma transplanted tumor and downregulated the level of MMP-9 protein. Meanwhile, the B16-F10 cells were used to study in vitro. The results showed that GBEE inhibited the proliferation and migration of B16-F10 cells. Simultaneously, it suppressed the heterogeneous adhesion of B16-F10 cells to human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. In addition, the levels of p-PI3K, p-Akt, NF-κB, and MMP-9 were decreased, while the PI3K and Akt were not significantly changed. These results indicate that GBEE can inhibit the metastasis of B16-F10 melanoma via multiple links and the molecular mechanism involved the regulation of PI3K/Akt/NF-κB/MMP-9 signaling pathway.

Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines

2016 ◽  
Vol 41 (6) ◽  
Author(s):  
Harika Atmaca ◽  
Emir Bozkurt ◽  
Aslı Kısım ◽  
Rüçhan Uslu
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cultured Cells ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Xtt Assay ◽  
Concentration Dependent Manner ◽  
End Point

AbstractObjective:In vitro preliminary oncological and translational studies are mainly based on evaluating the cytotoxic effects of a specific compound on cultured cells. Resveratrol is a commercially available compound which is originally isolated from the roots of white hellebore and later fromMethods:XTT end point assay and real-time cell based xCELLigence system were used to evaluate cytotoxicity. Cytotoxicity results were verified by monitoring cells under phase-contrast microscope which were treated with ICResults:Resveratrol decreased cell viability in a time- and concentration-dependent manner in all cancer cell lines when tested by both the XTT assay and xCELLigence system. Standard deviations of the xCELLigence data were found to be lower than the data from XTT assay.Conclusion:The data from this study strongly imply that xCELLigence system has higher precision, more enlightening and more reproducible than XTT end point assay.

scholarly journals 2-Hydroxy-4-Methylbenzoic Anhydride Inhibits Neuroinflammation in Cellular and Experimental Animal Models of Parkinson’s Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8195
Author(s):  
Soo-Yeol Song ◽  
In-Su Kim ◽  
Sushruta Koppula ◽  
Ju-Young Park ◽  
Byung-Wook Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Parent Compound ◽  
Intraperitoneal Administration ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Protein Levels

Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson’s disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinflammatory effects of HMA (0.1, 1.0, and 10 μM) were mediated by phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) in LPS-stimulated BV-2 cells. In vivo evaluations revealed that intraperitoneal administration of potent neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg, four times a 1 day) in mice resulted in activation of microglia in the brain in association with severe behavioral deficits as assessed using a pole test. However, prevention of microglial activation and attenuation of Parkinson’s disease (PD)-like behavioral changes was obtained by oral administration of HMA (30 mg/kg) for 14 days. Considering the overall results, our study showed that HMA exhibited strong anti-neuroinflammatory effects at lower concentrations than its parent compound. Further work is warranted in other animal and genetic models of PD for evaluating the efficacy of HMA to develop a potential therapeutic agent in the treatment of microglia-mediated neuroinflammatory disorders, including PD.

scholarly journals Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4302
Author(s):  
Xiao-Long Sun ◽  
Mei-Lin Zhu ◽  
Yi-Qun Dai ◽  
Hong-Mei Li ◽  
Bo-Han Li ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
Human Cancer Cell Lines

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

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