VP16-213 and podophyllotoxin. A study on the relationship between chemical structure and biological activity.
VP16-213, a semi-synthetic derivative of podophyllotoxin, is an effective antitumor agent in the treatment of a variety of leukemias and solid tumors. A comparison of the mechanism of action of VP16-213 and podophyllotoxin has revealed that although both drugs inhibit the uptake of nucleosides into HeLa cells, they exhibit other biological properties which are quite distinct. Podophyllotoxin is a potent inhibitor of microtubule assembly in vitro, while VP16-213 has no effect in this system. VP16-213 induces single stranded breaks in HeLa cells DNA, an effect which may be related to its antitumor activity. In contrast to VP16-213 treated cells, podophyllotoxin-treated cells maintain DNA integrity. Structure-activity relationship studies have identified some of chemical sites of VP16-213 and podophyllotoxin responsible for each of their biological properties. These studies illustrate that chemical modification of podophyllotoxin can generate derivatives which possess new and unique biological properties.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D005047:Etoposide / Q000031:analogs & derivatives / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008968:Molecular Conformation; D009705:Nucleosides / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013713:Teniposide / Q000031:analogs & derivatives
D009705:Nucleosides; D005047:Etoposide; D004247:DNA; D013713:Teniposide; D011034:Podophyllotoxin