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

Abstract

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.

Antihypertensive Effects of Flavonoids Isolated from Brazilian Green Propolis in Spontaneously Hypertensive Rats

“…24) Jeong et al have suggested that flavonoids with 3-OH group play a positive role in antioxidant activities. 25) Thus, it is well known that there are differences in the anti-oxidative revitalization and anti-inflammatory actions according to the structure of the B ring of flavonoids. The observation that these four flavonoids from Brazilian green propolis have a 4Ј-methoxyl group in the B ring is probably related to the antihypertensive activity.…”

SENYAWA INHIBITOR Α-Glukosidase DAN ANTIOKSIDAN DARI KUMIS KUCING DENGAN PENDEKATAN METABOLOMIK BERBASIS FTIR

“…Semakin banyak gugus hidroksi pada struktur kimia semakin tinggi aktivitas antioksidan oleh senyawa tersebut (Liu et al, 2010). Sebaliknya, flavonoid yang disubtitusi dengan sejumlah metoksi menunjukkan penurunan aktivitas antioksidan (Jeong et al, 2007). Senyawa diterpen ditandai dengan adanya pita serapan gugus hidroksil pada bilangan gelombang 3500-3480 cm -1 , ester karbonil pada bilangan gelombang 1270-1150 cm -1…”

Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways

“…Stable free radical scavenging activity Stable free radical scavenging activity was identified using the method reported by Jeong et al [24] . Briefly, 100 μmol/L of DPPH radical solution was dissolved in 100% ethanol.…”