RT Journal Article
SR Electronic
T1 A Comparison of Potency of Hydantoins in Metaphase Arrest and Inhibition of Microtubular Polymerization
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 275
OP 278
VO 17
IS 2
A1 ARCHIE A. MACKINNEY
A1 RAMLAL VYAS
A1 CAROLYN MUELLER
A1 CHERNA GORDER
YR 1980
UL http://molpharm.aspetjournals.org/content/17/2/275.abstract
AB 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.