ANTIMICROTUBULAR EFFECT OF CALVATIC ACID AND OF SOME RELATED-COMPOUNDS

A structure-activity relationship has been established between calvati c acid and some related synthetic compounds, and their ability to inhi bit GTP-induced microtubular protein polymerization in vitro. These co mpounds were effective in a dose- and a time-dependent manner. The mos t active drug was the p-chloro substituted compound, which showed its inhibitory activity without any preincubation period, which the others needed. Since if cysteine was present, polymerization was no longer a ffected, an involvement of titratable -SH groups of tubulin could be s uggested. In contrast, taxol-induced polymerization was only slightly inhibited by these compounds, and colchicine-binding activity was not generally impaired.