Cytotoxic flavonoids

Hirobe, C. et al.. Cytotoxic flavonoids from Vitex agnus-castus, Phytochemistry, 46, 521, 1997. 

Ismail, N. and Alam, M., A novel cytotoxic flavonoid glycoside from Physalis angulata, Fitoter-apia, 72, 676, 2001. 

Shi, Y.-Q. et al., Cytotoxic flavonoids with isoprene groups from Morus mongolica, J. Nat. Prod., 64, 181, 2001. 

Dumontet, V. et al.. New cytotoxic flavonoids from Cryptocarya infectoria. Tetrahedron, 57, 6189, 2001. 

Several types of bioactive compounds have been reported from the genus Broussonetia including glycosidase inhibitory alkaloids and aromatase inhibitory or cytotoxic flavonoids. This chapter reviews the biologically active constituents from the genus Broussonetia reported by the end of 2001. 

Isoflavonoids are also compounds that should be bom in mind for future cytotoxic studies with flavonoids. Isoflavones (aglycones with a 2-3 double bound, a 4 oxo group and the B-ring at C3 position) with the association of substituents mentioned above are not studied and could be. Besides, rotenoids are very cytotoxic isoflavonoids that are not well studied although one of them, 12a 3-hydroxyamorphigenin, is the most cytotoxic flavonoid found in our review, with values of less than 0.001 pg/mL on the six human cancer cell lines tested by Li et a/. [78]. 

The present work compiles the available literature about flavonoids inhibiting cancer cell lines and studies which structural requisites are important to increase the cytotoxic activity of these kind of compounds, to obtain a working hypothesis to help to rationalize the development of flavonoids as antitumor agents. The limited understanding found in the literature about a possible stmcture-activity relationship is due, in our opinion, to that when the influence of a substituent in a determined position has been studied, the presence of other substituents in other position has not been taken into account. So, we have studied associations of substituents and, based on the studied literature, we have dared to propose possible cytotoxic flavonoids that we have not found in our review. Finally we suggest that isoflavonoids are little studied compounds that should be bom in mind for future antitumor studies with flavonoids. 

Some cytotoxic flavonoids were isolated from Scutellaria indica [25] these were 2(S)-5,7-dihydroxy-8,2 -dimethoxyflavanone (50), 2(S)-5,7,2 -trihydroxy-8-methoxyflavanone (51), 2(S)-5,2 ,5 -trihydroxy-7,8-dimethoxyflavanone (52) and wogonin (5,7-dihydroxy-8-methoxy-flavone) (53), 5,7-dihydroxy-8,2 -dimethoxyflavone (54). 

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