GLUCOSYLATION OF CYCLODEXTRIN-COMPLEXED PODOPHYLLOTOXIN BY CELL-CULTURES OF LINUM-FLAVUM L

The glucosylation of the cytotoxic lignan podophyllotoxin by cell cult ures derived from Linum flavum was investigated. Four cyclodextrins: b eta-cyclodextrin, gamma-cyclodextrin, dimethyl-beta-cyclodextrin and h ydroxypropyl-beta-cyclodextrin were used to improve the solubility of podophyllotoxin by complexation. Dimethyl-beta-cyclodextrin met our ne eds the best and the solubility of podophyllotoxin could be enhanced f rom 0.15 to 1.92 mM, using a podophyllotoxin/cyclodextrin ratio of 1:1 . Growth parameters of the cell suspensions were not affected neither by the addition of cyclodextrins alone, nor when complexed podophyllot oxin was dissolved in the medium. The complexed lignan disappeared rap idly from the culture medium, within 24 h, under all experimental cond itions. Almost simultaneously, between 73 and 100% of detectable podop hyllotoxin was bioconverted into podophyllotoxin-beta-D-glucoside. A m aximal bioconversion rate of 0.51 mmol l-1 suspension day-1 was calcul ated for the L. flavum cells growing in a medium which included the po dophyllotoxin/dimethyl-beta-cyclodextrin complex at a final concentrat ion of 1.35 mM.