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

Affiliation

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.

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