Polyoxygenated Flavones; Synthesis, Cytotoxicities and Antitumor Activity against ICR Mice Carrying S-180 Cells

Fitty two flavones were synthesized from polyoxygenated dibenzoylmethanes which were obtained by a modified Baker-Venkatarman rearrangement, of 2-benzoyl oxyacetophenones. The following flavones among them showed good cytotoxic activities against L1210 and HL60 cells ; 2'-benzoyloxy-5,7-dimethoxyflavone $(8.2{\mu}g/ml,{\;}5.0 {\mu}g/ml)$, 2'-benzyloxy-5,7,8-trimethoxyflavone $(5,9 {\mu}g/ml,{\;}11.0{\mu}g/ml,{\;}2.7{\mu}g/ml)$, 2'-hydroxy-5,7,8-trimethoxyflavone $(9.8{\mu}/ml,{\;}6.2{\mu}g/ml)$, 2'-benzyloxy-5-hydroxyflavone $(5.2 {\mu}g/ml,{\;}3.6{\mu}g/ml)$, and 5,2'-dihydroxyflavone $(5.1{\mu}g/ml,{\;}4.0{\mu}g/ml)$. Presence of 5-methoxy group potentiated the cytotoxic activity, while the existence of 7-methoxy group decreased the activity. 5-Hydroxy or methoxy activates 4-carbonyl group, while 7-methoxy group deactivates the acrbonyl group. From these observation it was concluded that the activation of carbonyl group at C-4 of a flavone is important for the enahncement of the cytotoxic activity. The presence of both 5-hydroxy and 2-benzyloxy-or 2-hydroxy group enhanced the antitumor activity; 2'-benzyloxy-5-hydroxy-7-methoxyflaone 9T/C=144%), 5.2'-dihydroxy-7-methoxyflavone (T/C=132%) and 5,2'-dihydroxy-6,78,6' trtramethoxyflvone (T/C = 172%) 2'hexanolytion of 5,2'-dihydroxy-flavones did not improve the natitumor activity; 2' hexanoyloxy-5-hydroxy-7-methoxyflavone showed T/C = 132%, about the same as that of 5,2'-dihydroxy-7-methoxyflvone (T/C=130%)