Inhibitors of Bacillus subtilis DNA polymerase III. Structure-activity relationships of 6-(phenylhydrazino)uracils

J Med Chem. 1977 Sep;20(9):1181-5. doi: 10.1021/jm00219a014.


6-(Phenylhydrazino)uracils inhibit the replication-specific enzyme DNA polymerase III of Bacillus subtilis by forming a strong, reversible complex with template-primer DNA and enzyme. The phenyl ring interacts with a hydrophobic enzyme site which, on the basis of structure-activity relationships of substituted analogues, appears to possess the following characteristics: (1) planarity or near-planarity; (2) a finite capacity to accommodate bulky substituents; and (3) location near the domain of the enzyme active site. A mutant DNA polymerase III, derived from a mutant strain of B. subtilis selected for resistance to 6-(p-hydroxyphenylazo)pyrimidines, is resistant only to inhibitors bearing p-hydroxy or amino groups and is hypersensitive to inhibitors containing nonpolar substituents; these results suggest the existence of mutable, secondary regions of the binding site which interact with para substituents and, thus, influence the strength of the primary phenyl-enzyme interaction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacillus subtilis / enzymology*
  • Binding Sites
  • DNA Polymerase III / antagonists & inhibitors*
  • Nucleic Acid Synthesis Inhibitors*
  • Phenylhydrazines / pharmacology*
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology


  • Nucleic Acid Synthesis Inhibitors
  • Phenylhydrazines
  • Uracil
  • DNA Polymerase III