Inhibition of herpes simplex virus type 1 helicase-primase by (dichloroanilino)purines and -pyrimidines

  • J Med Chem. 1995 May 12;38(10):1820-5. doi: 10.1021/jm00010a027.
J J Crute  1 ,  I R Lehman ,  J Gambino ,  T F Yang ,  P Medveczky ,  M Medveczky ,  N N Khan ,  C Mulder ,  J Monroe ,  G E Wright
Affiliations
  • 1. Department of Biochemistry, Stanford University Medical School, California 94305, USA.
PMID: 7752206 DOI: 10.1021/jm00010a027
Abstract

Herpes simplex virus type 1 (HSV1) encodes a heterotrimeric helicase-primase comprised of the products of three of the seven DNA replication-specific genes. Several dihalo-substituted derivatives of N2-phenylguanines and 2-anilinoadenines weakly inhibited the intrinsic DNA-dependent NTPase activity of the HSV1 helicase-primase, and these compounds inhibited the DNA-unwinding activity of the enzyme. The primase activity of the enzyme was strongly inhibited by 3,4- and 3,5-dichloroanilino derivatives of adenine and 2-aminopyrimidines. These compounds and nucleoside analogs of 2-(3,5-dichloroanilino)purines inhibited viral DNA synthesis in HSV1-infected HeLa cells in culture but also inhibited cellular DNA synthesis, likely as a result of inhibition of cellular primase and/or DNA polymerases.