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Molecular Pharmacology, Vol 17, 275-278, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

A Comparison of Potency of Hydantoins in Metaphase Arrest and Inhibition of Microtubular Polymerization

ARCHIE A. MACKINNEY 1, RAMLAL VYAS 1, CAROLYN MUELLER 1, and CHERNA GORDER 1

1 Hematology Research Laboratory, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, Wisconsin 53705

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.

Note:
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.

Submitted on April 30, 1979
Accepted on November 8, 1979




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