Anti-herpesvirus activity of citrusinine-I, a new acridone alkaloid, and related compounds.

Abstract:

:Citrusinine-I, a new acridone alkaloid isolated from the root bark of the citrus plant (Rutaceae), exhibited potent activity against herpes simplex virus (HSV) type 1 and type 2 at low concentrations relative to their cytotoxicity; 50% effective concentrations (ED50) of citrusinine-I were 0.56 micrograms/ml and 0.74 micrograms/ml against HSV-1 and HSV-2, respectively. Inhibitory action was also demonstrated against cytomegalovirus (CMV) and thymidine kinase-deficient or DNA polymerase mutants of HSV-2. The compound markedly suppressed HSV-2 and CMV DNA synthesis at concentrations which did not inhibit the synthesis of virus-induced early polypeptides. However, citrusinine-I had no inhibitory activity against HSV and CMV DNA polymerases in cell-free extracts. Although the target of this inhibitor remains to be elucidated, the most plausible candidate is a virus-coded ribonucleotide reductase. Citrusinine-1, when combined with acyclovir or ganciclovir, synergistically potentiated the antiherpetic activity of these agents. Based on a comparative study of the antiherpetic activity of citrusinine-1 and 28 related compounds, a structure-activity relationship could be established.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Yamamoto N,Furukawa H,Ito Y,Yoshida S,Maeno K,Nishiyama Y

doi

10.1016/0166-3542(89)90065-x

subject

Has Abstract

pub_date

1989-08-01 00:00:00

pages

21-36

issue

1

eissn

0166-3542

issn

1872-9096

pii

0166-3542(89)90065-X

journal_volume

12

pub_type

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