PMID- 16650489
OWN - NLM
STAT- MEDLINE
DCOM- 20061103
LR  - 20240109
IS  - 0166-3542 (Print)
IS  - 0166-3542 (Linking)
VI  - 72
IP  - 1
DP  - 2006 Oct
TI  - Antiviral properties of new arylsulfone derivatives with activity against human 
      betaherpesviruses.
PG  - 60-7
AB  - Based on our previous experience with arylsulfone derivatives displaying 
      antiherpetic activity, we synthesized several analogues in which the sulfonyl 
      group is part of a bicyclic structure. The benzene-fused derivative 
      2H-3-(4-chlorophenyl)-3,4-dihydro-1,4-benzo-thiazine-2-carbonitrile 1,1-dioxide 
      and its thiophene-fused analogue were shown to have favorable activity and 
      selectivity against the betaherpesviruses human cytomegalovirus (HCMV) and human 
      herpesvirus 6 (HHV-6) and 7 (HHV-7). The benzene-fused derivative retained its 
      anti-HCMV activity when evaluated against virus strains resistant to foscarnet, 
      ganciclovir, and/or cidofovir. The compound conferred >or=95% inhibition of viral 
      DNA synthesis in HHV-6-infected cells. RT-PCR analysis of immediate-early, early 
      and late gene products revealed that this arylsulfone compound acts at a step 
      preceding late gene expression, and coinciding with the inhibition exerted by 
      foscarnet. No inhibitory effect was seen in an enzyme assay for DNA elongation 
      catalyzed by the HCMV or HHV-6 DNA polymerase catalytic subunit. The arylsulfone 
      derivatives had no effect on the functional interaction between the catalytic 
      subunit of HCMV DNA polymerase and its accessory protein, nor did they disrupt 
      the physical interaction between the two proteins. We conclude that these 
      arylsulfone derivatives represent new betaherpesvirus inhibitors with a novel 
      mode of action that results in indirect inhibition of viral DNA synthesis.
FAU - Naesens, Lieve
AU  - Naesens L
AD  - Rega Institute for Medical Research, Katholieke Universiteit Leuven, 
      Minderbroedersstraat 10, B-3000 Leuven, Belgium. 
      lieve.naesens@rega.kuleuven.ac.be
FAU - Stephens, Chad E
AU  - Stephens CE
FAU - Andrei, Graciela
AU  - Andrei G
FAU - Loregian, Arianna
AU  - Loregian A
FAU - De Bolle, Leen
AU  - De Bolle L
FAU - Snoeck, Robert
AU  - Snoeck R
FAU - Sowell, J Walter
AU  - Sowell JW
FAU - De Clercq, Erik
AU  - De Clercq E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060418
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Sulfones)
RN  - 364P9RVW4X (Foscarnet)
SB  - IM
MH  - Antiviral Agents/chemistry/*pharmacology
MH  - Cell Line
MH  - Cytomegalovirus/*drug effects/genetics
MH  - DNA, Viral/biosynthesis/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Foscarnet/pharmacology
MH  - Herpesvirus 6, Human/drug effects/genetics
MH  - Herpesvirus 7, Human/drug effects
MH  - Humans
MH  - Sulfones/chemistry/*pharmacology
EDAT- 2006/05/03 09:00
MHDA- 2006/11/04 09:00
CRDT- 2006/05/03 09:00
PHST- 2005/11/29 00:00 [received]
PHST- 2006/03/27 00:00 [revised]
PHST- 2006/03/28 00:00 [accepted]
PHST- 2006/05/03 09:00 [pubmed]
PHST- 2006/11/04 09:00 [medline]
PHST- 2006/05/03 09:00 [entrez]
AID - S0166-3542(06)00092-1 [pii]
AID - 10.1016/j.antiviral.2006.03.013 [doi]
PST - ppublish
SO  - Antiviral Res. 2006 Oct;72(1):60-7. doi: 10.1016/j.antiviral.2006.03.013. Epub 
      2006 Apr 18.