Cytotoxic and antioxidant effects of methoxylated stilbene analogues on HepG2 hepatoma and Chang liver cells: Implications for structure activity relationship

Stilbenes possess a variety of biological activities including chemopreventive activity. This study was conducted to evaluate the structural activity relationships of six methoxylated stilbene analogues with respect to their cytotoxic effects and antioxidant activities on HepG2 hepatoma and Chang liver cells. The cytotoxic and total antioxidant activities of six stilbene analogues were determined by MTT and Ferric Reducing Antioxidant Power (FRAP) assays, respectively. We found that the cis-methoxylated stilbene: (Z)-3,4,4'-trimethoxystilbene was the most potent and selective antiproliferative agent (IC50 89 µM) in HepG2 cells. For the total antioxidant activity, compounds possessing hydroxyl groups at the 4' position namely (E)-3-methoxy-4'-hydroxystilbene, (E)-3,5-dimethoxy-4'-hydroxystilbene (pterostilbene), (E)-4-methoxy-4'-hydroxystilbene showed the highest antioxidant activity. Structure activity relationship studies of these compounds demonstrated that the cytotoxic effect and antioxidant activities of the tested compounds in this study were structurally dependent.

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CYTOTOXIC AND ANTIOXIDANT ACTIVITIES OF SECONDARY METABOLITES FROM PULICARIA UNDULATA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i9.12814 ◽

2016 ◽

Vol 8 (9) ◽

pp. 150 ◽

Cited By ~ 6

Author(s):

Taha A. Hussien ◽

Sayed A. El-toumy ◽

Hossam M. Hassan ◽

Mona H. Hetta

Keyword(s):

Antioxidant Activity ◽

Secondary Metabolites ◽

Antioxidant Activities ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Hep G2 ◽

Structure Activity ◽

Dpph Method ◽

Mcf 7

Objective: To evaluate the in vitro cytotoxicity, antioxidant activities and structure-activity relationship of secondary metabolites isolated from Pulicaria undulata.Methods: The methylene chloride-methanol (1:1) extract of the air-dried aerial parts of Pulicaria undulata was fractionated and separated to obtain the isolated compounds by different chromatographic techniques. Structures of the isolated compounds were determined on the basis of the extensive spectroscopic analysis, including 1D and 2D NMR and compared with the literature data. The crude extract and the isolated compounds were evaluated for in vitro antioxidant activity using the 2,2 diphenyl dipicryl hydrazine (DPPH) method and cytotoxic assay using human breast cancer (MCF-7) and hepatoma (Hep G2) cell line.Results: Nine secondary metabolites were isolated from Pulicaria undulata in this study. Of which two terpenoidal compounds; 8-epi-ivalbin and 11β, 13-dihydro-4H-xanthalongin 4-O-β-D-glucopyranoside firstly isolated from the genus pulicaria and three flavonoids; eupatolitin, 6-methoxykaempferol, and patulitrin firstly isolated from P. undulata. 6-methoxykaempferol (IC50 2.3 µg/ml) showed the most potent antioxidant activity. The highest cytotoxic effect against MCF-7 and Hep G2 cells was obtained with eupatolitin (IC50 27.6 and 23.5 µg/ml) respectively. The structure-activity relationship was also examined and the findings presented here showed that 3, 5, 7, 4' and 3, 5, 4', 5'-hydroxy flavonoids were potent antioxidant and has cytotoxic activity.Conclusion: Pulicaria undulata is a promising medicinal plant, and our study tends to support the therapeutic value of this plant as antioxidant drug and in the treatment of cancer.

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Antioxidant and Chemosensitizing Effects of Flavonoids with Hydroxy and/or Methoxy Groups and Structure-Activity Relationship

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3kw2z ◽

2007 ◽

Vol 10 (4) ◽

pp. 537 ◽

Cited By ~ 41

Author(s):

Ju-Mi Jeong ◽

Cheol-Hee Choi ◽

Su-Kyeong Kang ◽

In-Hwa Lee ◽

Ji-Yoon Lee ◽

...

Keyword(s):

Antioxidant Activity ◽

Antioxidant Activities ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Oh Groups ◽

Structure Activity ◽

P Glycoprotein ◽

Ic50 Values

Purpose. Flavonoids have been used as antioxidant, chemopreventive and chemosensitizing agents. In this study, eleven flavonoids containing a variety of hydroxy (OH) and/or methoxy (OMe) groups were evaluated for their antioxidant, cytotoxic and chemosensitizing effects to create a structure-activity relationship (SAR). Methods. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical solution-based chemical assay and and 2',7'-dichlorofluorescin diacetate (DCFH-DA) cellular-based assay were used to compare the free radical scavenging activity on the same molar concentration basis using the AML-2/DX100 cells which are characterized by the down-regulated expression of catalase and resulting supersensitiviy to hydrogen peroxide. The chemosensitization and cytotoxicity were determined by the MTT assay in the presence or absence of an anticancer drug using the P-glycoprotein-overexpressing AML-2 subline AML-2/D100 cells. Results. The antioxidant activity of the flavonoid (3,5,7,3’,4’-OH) was higher than that of the flavonoid (5,7,3’,4’-OH). Flavonoids substituted with the various number of OMe decreased antioxidant activity. Flavonoids with 7-OH or 5,7-OH groups have the highest cytotoxicity, and flavonoids with 5,7-OMe group intermediate cytotoxicity. The IC50 values of flavonoid (5,7-OMe, 3’,4’,5’-OMe) and flavonoid (5,7-OMe, 4’-OMe), 0.4 M and 1.4 M. The IC50 values of flavonoid (5,6,7-OMe, 3’,4’-OMe) and flavonoid (5,6,7-OMe, 3’,4’,5’-OMe), 3.2 uM and 0.9 M, respectively, and those of flavonoid (5,6,7-OMe, 3’,4’,5’-OMe) and flavonoid (5,7-OMe,3’,4’,5’-OMe) were 0.9 M and 0.4 M, respectively. Conclusions. These results suggest that flavonoids with 3-OH group play a positive role in antioxidant activities, flavonoids with 5-OH and/or 7-OH groups show the higher cytotoxicity, and flavonoids with 3’-OMe and/or 5’-OMe groups plays positive but 6-OMe groups negative roles in the P-glycoprotein (Pgp) inhibition. It is believed that these SAR results can be taken into account for the development of flavonoids with high therapeutic index.

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Flavonoids from the Genus Euphorbia: Isolation, Structure, Pharmacological Activities and Structure–Activity Relationships

Pharmaceuticals ◽

10.3390/ph14050428 ◽

2021 ◽

Vol 14 (5) ◽

pp. 428

Author(s):

Douglas Kemboi Magozwi ◽

Mmabatho Dinala ◽

Nthabiseng Mokwana ◽

Xavier Siwe-Noundou ◽

Rui W. M. Krause ◽

...

Keyword(s):

Therapeutic Potential ◽

Antioxidant Properties ◽

Structure Activity Relationship ◽

Biological Properties ◽

Therapeutic Agents ◽

Skeletal Structure ◽

Activity Relationship ◽

Hydroxyl Groups ◽

Structure Activity ◽

Review Reports

Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship of Euphorbia flavonoids for the period covering 2000–2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure–activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents.

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Synthesis and Antioxidant Activity of Modified (+)-Catechin Derivatives. Structure-Activity Relationship

American Journal of Food Technology ◽

10.3923/ajft.2007.618.629 ◽

2007 ◽

Vol 2 (7) ◽

pp. 618-629 ◽

Cited By ~ 4

Author(s):

Nour-Eddine Es-Safi ◽

Josiane Beauhaire ◽

Christine Le Guerneve ◽

Paul-Henri Ducrot

Keyword(s):

Antioxidant Activity ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Structure Activity

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Antioxidant Activity of 1’-Hydroxyethylnaphthazarins and their Derivatives

Natural Product Communications ◽

10.1177/1934578x1701201218 ◽

2017 ◽

Vol 12 (12) ◽

pp. 1934578X1701201

Author(s):

Natalia K. Utkina ◽

Natalia D. Pokhilo

Keyword(s):

Antioxidant Activity ◽

Radical Cation ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Hydroxyl Group ◽

Side Chains ◽

Scavenging Activity ◽

Structure Activity

The ABTS•+ radical cation scavenging activity of known (2-5, 9, 10) and new (6-8) 1’-hydroxyethylnaphthazarins and their products of esterification and etherification was evaluated and a structure-activity relationship was studied. It was shown, that the structure of side chains does not affect the radical scavenging activity of 1’-hydroxyethylnaphthazarins and their derivatives. The presence of methoxyl groups on the naphthazarin core slightly enhanced the antioxidant activity of compounds compared with compounds without methoxyl groups. The presence of the additional hydroxyl group on the naphthazarin moiety of isonorlomazarin (5) and its derivative (6) is essential for the activity.

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