scholarly journals HCV Protease Inhibitory, Cytotoxic and Apoptosis-Inducing Effects of Oleanolic Acid Derivatives

2009 ◽  
Vol 12 (3) ◽  
pp. 243 ◽  
Author(s):  
Chao-Mei Ma ◽  
Xiu-Hong Wu ◽  
Masao Hattori ◽  
Xi-Jun Wang ◽  
Yoshihiro Kano
Keyword(s):  
Oleanolic Acid ◽  
Inhibitory Activity ◽  
Free Amino ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Cytotoxic Effects ◽  
Hcv Protease ◽  
Amino Derivatives ◽  
Chain Lengths ◽  
Derivatives Of

Purpose: To evaluate oleanolic acid derivatives on liver disease related bioactivities, 29 oleanolic acid derivatives of several series were tested for their inhibitory activity on hepatitis C viral protease and for their cytotoxic effects on Hep G2 cells. Results: The amino derivatives showed potent cytotoxicity, among which, the beta-amino isomer exhibited more distinct cytotoxicity than the alpha-isomer. The cytotoxicity of hemiesters and hemiamides varied as the chain lengths varied. The oxalic and malonic hemiesters showed weaker cytototoxicity than oleanolic acid, while those with longer chain lengths showed higher cytotoxicity. Contrary to the cytotoxic activity, the free amino derivatives showed little inhibitory activity on HCV protease. All the hemiesters and hemiamides showed high activity against HCV protease. Conclusion: The results suggest that adding free amino group(s) to the skeletons of triterpenes may be an effective way of synthesis of anti-tumor compounds. Adding acidic groups to triterpene skeletons may be an effective way for producing anti-viral compounds.

scholarly journals Bioactive Compounds from Monotheca Buxifolia Inhibit the Growth of Hepatocellular Carcinoma Cells

2020 ◽  
Author(s):  
Said Hassan ◽  
Ashfaq Rehman ◽  
Syed Babar Jamal ◽  
Yaqin Liu ◽  
Shaoyong Lu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Oleanolic Acid ◽  
Bioactive Compounds ◽  
Lauric Acid ◽  
Active Site ◽  
Annexin V ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Monotheca Buxifolia ◽  
Ethylhexyl Phthalate

The natural products and conventional chemotherapeutic drugs are believed to increase the cure rates of anti-cancer treatment while reducing their toxicity. The current study investigates the cytotoxic and apoptogenic effects of bioactive compounds from Monotheca buxifolia on Hep G2 cell lines. The effect on the viability of Hep G2 cells was evaluated by MTT assay; Morphological changes were studied, the apoptotic activity was demonstrated through Annexin-V-FITC/ PI, a molecular dynamics simulation study was conducted to explore the binding pattern of the compounds in the active site of the PPRAδ protein. The isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells, as determined by MTT assay and annexin V-FITC/PI. The IC50 value for lauric acid was 56.4584 ± 1.20 µg/ml, that for oleanolic acid was 31.9421 ± 1.03 µg/ml, and that for bis(2-ethylhexyl) phthalate was 83.8019 ± 2.18 µg/ml. After 24 h of treatment, 29.5% of Hep G2 cells treated with lauric acid, 52.1% of those treated with oleanolic acid, and 22.4% of those treated with bis(2-ethylhexyl) phthalate were apoptotic. Morphological assay and Hoechst staining microscopy revealed the morphological alterations of cell membrane accompanied by nuclear condensation after treatment. The high fluctuation indicates the high potency and adopting various interactions, and vice versa, the oleanolic acid showed highly residues fluctuation, which remains stable in the active site of PPARδ protein and involved in various interactions while remaining locally fluctuated in the binding site the other two compounds. In conclusion, a significant apoptogenic effect was exhibited by lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate against HepG2 cells in inducing apoptosis. Our findings indicate that these bioactive compounds hold promise as potential therapeutic for hepatocellular carcinoma.

Characterization of Monocyte-Associated Factor V

1993 ◽  
Vol 70 (02) ◽  
pp. 273-280 ◽  
Author(s):  
Janos Kappelmayer ◽  
Satya P Kunapuli ◽  
Edward G Wyshock ◽  
Robert W Colman
Keyword(s):  
Monoclonal Antibody ◽  
Light Chain ◽  
Peripheral Blood ◽  
De Novo ◽  
Factor V ◽  
Blood Monocytes ◽  
De Novo Synthesis ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Peripheral Blood Monocytes

SummaryWe demonstrate that in addition to possessing binding sites for intact factor V (FV), unstimulated peripheral blood monocytes also express activated factor V (FVa) on their surfaces. FVa was identified on the monocyte surface by monoclonal antibody B38 recognizing FVa light chain and by human oligoclonal antibodies H1 (to FVa light chain) and H2 (to FVa heavy chain) using immunofluorescence microscopy and flow cytometry. On Western blots, partially cleaved FV could be identified as a 220 kDa band in lysates of monocytes. In addition to surface expression of FVa, monocytes also contain intracellular FV as detected only after permeabilization by Triton X-100 by monoclonal antibody B10 directed specifically to the Cl domain not present in FVa. We sought to determine whether the presence of FV in peripheral blood monocytes is a result of de novo synthesis.Using in situ hybridization, no FV mRNA could be detected in monocytes, while in parallel control studies, factor V mRNA was detectable in Hep G2 cells and CD18 mRNA in monocytes. In addition, using reverse transcriptase and the polymerase chain reaction, no FV mRNA was detected in mononuclear cells or in U937 cells, but mRNA for factor V was present in Hep G2 cells using the same techniques. These data suggest that FV is present in human monocytes, presumably acquired by binding of plasma FV, and that the presence of this critical coagulation factor is not due to de novo synthesis.

Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

2019 ◽  
Vol 19 (13) ◽  
pp. 1093-1110 ◽  
Author(s):  
Adel A.H. Abdel Rahman ◽  
Ibrahim F. Nassar ◽  
Amira K.F. Shaban ◽  
Dina S. EL-Kady ◽  
Hanem M. Awad ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Human Liver ◽  
Docking Studies ◽  
Cyclin Dependent Kinase ◽  
Binding Interaction ◽  
Enzyme Active Site ◽  
Human Liver Cancer ◽  
Amino Derivatives ◽  
Activity Behavior ◽  
Derivatives Of

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

Thermal cyclocondensations of 3-N(4- and 5-benzimidazolyl and benztriazolyl)amino derivatives of 2-propenoic acid

1987 ◽  
Vol 52 (12) ◽  
pp. 2918-2925 ◽  
Author(s):  
Viktor Milata ◽  
Dušan Ilavský
Keyword(s):  
Uv Spectra ◽  
Propenoic Acid ◽  
Amino Derivatives ◽  
Derivatives Of ◽  
C Nmr ◽  
Ir And Uv Spectra

The cyclization of 3-N(4- and 5-benzimidazolyl and benztriazolyl)amino-2-cyano- and 2-ethoxycarbonyl-2-propenoate esters Ia, b-IVa, b under the conditions of the Gould-Jacobs reaction leads to angularly ring-fused substituted imidazo or triazolo[4,5-f] (V, VI) and [4,5-h] (VII, VIII) quinolines, respectively. The esters Vb-VIIIb have been transformed into the corresponding chloroderivatives Vc-VIIIc. 3-N(5-Benzimidazolyl and 5-benztriazolyl)amino-2-cyano-2-propenenitriles are cyclized in the presence of aluminium(III) chloride to give the aminoquinolines Vd, VId. The structure of the products has been characterized by their 1H, 13C NMR, IR, and UV spectra.

Glutamic Acid Uptake Inhibition Assay in Cultured Hep G2 Cells as an Alternative Method for Evaluating Potential In Vivo Eye Irritation

1989 ◽  
Vol 16 (4) ◽  
pp. 344-352
Author(s):  
Paul J. Dierickx
Keyword(s):  
Glutamic Acid ◽  
Corneal Opacity ◽  
Acid Uptake ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Eye Irritation ◽  
Uptake Inhibition ◽  
Range Finding ◽  
G2 Cells

Glutamic acid (GA) content was measured in cultured Hep G2 cells, after treatment of the cells with test compounds. The results with 37 chemicals were compared with their respective rabbit eye irritation data, of which 17 were determined according to the OECD test, and the other 20 in range-finding studies. The chemicals were mainly organic solvents (alcohols, esters, amines, acids and others). The xenobiotics were applied to the cells for 4 hours at 5 different concentrations. The cells were then incubated for 15 minutes with tritiated GA. GA uptake inhibition was measured by liquid scintillation counting, and the results were expressed as the GI50 value, which is the concentration of test compound required to induce a 50% reduction in GA uptake. A linear correlation coefficient r = 0.66 was found between the log GI50 and the mean corneal opacity scores. This value is comparable to that obtained in total protein and uridine uptake inhibition studies. However, r = 0.81 was found when the log GI50 was compared with range-finding scores, indicating that a closer relationship exists between cytotoxicity and the latter.

scholarly journals Human proapolipoprotein A-II is cleaved following secretion from Hep G2 cells by a thiol protease.

1984 ◽  
Vol 259 (24) ◽  
pp. 15556-15563 ◽  
Author(s):  
J I Gordon ◽  
H F Sims ◽  
C Edelstein ◽  
A M Scanu ◽  
A W Strauss
Keyword(s):  
Hep G2 ◽  
Hep G2 Cells ◽  
Thiol Protease ◽  
G2 Cells

The Hep G2 Cell Line as a Possible Alternative to Isolated Hepatocytes in Cytotoxicity Studies

1988 ◽  
Vol 16 (1) ◽  
pp. 16-22
Author(s):  
Marina Marinovich ◽  
Jose L. Lorenzo ◽  
Liliana M. Flaminio ◽  
Agnese Granata ◽  
Corrado L. Galli
Keyword(s):  
Cell Line ◽  
Rat Hepatocytes ◽  
Prostaglandin E ◽  
Human Hepatoma ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Isolated Rat Hepatocytes ◽  
G2 Cells ◽  
Isolated Rat

The hepatotoxicity of carbon tetrachloride (CC14) was evaluated in vitro in freshly isolated rat hepatocytes and in the human hepatoma cell line, Hep G2. Toxicity was assessed by the leakage of cytosolic enzymes (lactate dehydrogenase and aspartate aminotransferase) and cell viability (trypan blue exclusion). The established human cells were less sensitive to CCl4-induced injury; higher doses of the toxic agent and longer incubation times were necessary to elicit cell damage. Micromolar concentrations of prostaglandin E2 significantly decreased enzyme leakage in both Hep G2 cells and rat hepatocytes challenged with CC14; a stable derivative of prostacyclin (ZK 36374) was ineffective. These results suggest that human hepatoma Hep G2 cells may represent a valid alternative to isolated rat hepatocytes for an initial approach to the in vitro evaluation of cell toxicity.

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