VP16-213 and podophyllotoxin

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Abstract
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 cell 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 the 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.

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