Relevance of DNA binding to the mechanism of anti-herpesvirus activity of benzhydrazone.
Benzhydrazone (1H-benz(f)indene-1,3(2H)-dione bis (amidino-hydrazone) (BH) is a synthetic compound with selective anti-herpesvirus activity. Its selectivity seems to stem from the inhibition of viral protein glycosylation and several hypotheses have been formulated to explain such an effect. Data presented here demonstrate that DNA binding is a prominent feature of BH. Interaction is taking place with a relatively high affinity constant and is more efficient for GC-rich viral sequences. Experiments with the cloned DNA fragments from a BH-resistant virus strain indicate that BH-DNA complex formation is drastically reduced as compared to BH-sensitive virus. The occurrence of the resistant phenotype in HEp-2 cells but not in Vero cells could be explained by differences in BH cytotoxicity. Changes in drug uptake and accumulation by cells following infection, in addition to GC preference, may also account for the degree of antiviral selectivity shown by BH.
Institute of Microbiology, University of Padova, Italy.
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Palu
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Tognon
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Romanelli
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Rassu
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Parolin
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Zagotto
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Palumbo
D000818:Animals; D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D006835:Hydrazones / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D014176:Protein Biosynthesis; D018139:Simplexvirus / Q000187:drug effects* / Q000378:metabolism; D014709:Vero Cells
D004279:DNA, Viral; D006835:Hydrazones; C027566:benzhydrazone