Abstract
The effects of 11 hydantoins on the mitotic apparatus were compared in two assays: metaphase arrest and tubulin polymerization. Drugs were fitted into three of four classes: (1) metaphase arrest and inhibition of tubulin polymerization [DPH, HPPH, MPPH]; 2) inhibition of tubulin polymerization only (1,3-DiAc-DPH and 3-AcO-DPH); (3) no effect on either system (mesantoin, DHDH, 3-OH-DPH, coord, hydantoin, nirvanol); and (4) metaphase arrest only (no drugs found). Structure-function relationships favored an intact hydantoin ring and two benzene rings for activity in both assays. Although complete correlation was not found between the two assays, it appears that inhibition of tubulin polymerization is a necessary feature of metaphase arrest by hydantoins.
ACKNOWLEDGMENTS We thank Gary Girdonikas for performing mass and NMR spectroscopy on MPPH, Barbara McKnight for statistical analysis of the polymerization data, Cynthia Birch for editorial assistance, and Betty Schultz for library support.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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