Correlation of tubulin-binding and antitumor activities of podophyllotoxin analogs.

The tubulin-binding affinities of podophyllotoxin and 12 related compounds have been compared with the effectiveness of these drugs in three assays of antitumor activity: (1) The mastocytoma assay of inhibited tumor cell growth in vitro; (2) the 37 sarcoma assay of tumor remission in vivo; and (3) the Stentor regeneration inhibition assay which detects a requirement for microtubule polymerization. The results indicate that there is a positive Spearman rank correlation coefficient between the inhibition constant for the binding of colchicine to tubulin in the presence of these compounds and the effectiveness of the compounds in the three assays of tumor growth inhibition. It is suggested that tubulin-binding assays may be a useful step in the screening of podophyllotoxin-like compounds suspected of disrupting mitosis by binding to microtubule protein.