Inhibition of herpes simplex virus type 1 helicase-primase by (dichloroanilino)purines and -pyrimidines.
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.
Crute
J J
JJ
Department of Biochemistry, Stanford University Medical School, California 94305, USA.
Lehman
I R
IR
Gambino
J
J
Yang
T F
TF
Medveczky
P
P
Medveczky
M
M
Khan
N N
NN
Mulder
C
C
Monroe
J
J
Wright
G E
GE
D000814:Aniline Compounds; D000998:Antiviral Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004265:DNA Helicases / Q000037:antagonists & inhibitors*; D019915:DNA Primase; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D011687:Purines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*
D000814:Aniline Compounds; D000998:Antiviral Agents; D004279:DNA, Viral; D011687:Purines; D011743:Pyrimidines; D019915:DNA Primase; D012316:RNA Nucleotidyltransferases; D004265:DNA Helicases