PREPARATION AND CYTOTOXICITY OF PODOPHYLLOTOXIN DERIVATIVES LACKING THE LACTONE RING

Several cyclolignans lacking of the lactone moiety can easily be prepa red from naturally occurring lignans such as podophyllotoxin and deoxy podophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds sh ow similar effects in all the neoplastic systems tested, except the al dehyde 9 (methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate) and the hyd razones 16 and 17 which show a highly selective cytotoxicity towards H T-29 human colon carcinoma. Additionally, several molecular modeling s tudies have been done with aldehyde 9 and the corresponding saturated aldehyde 13 in comparison with podophyllotoxin. (C) 1997 Elsevier Scie nce Ltd.