PMID- 9875413
OWN - NLM
STAT- MEDLINE
DCOM- 19990210
LR  - 20071114
IS  - 0956-3202 (Print)
IS  - 0956-3202 (Linking)
VI  - 9
IP  - 4
DP  - 1998 Jul
TI  - (Z)- and (E)-2-(hydroxymethylcyclopropylidene)-methylpurines and pyrimidines as 
      antiviral agents.
PG  - 341-52
AB  - Several Z- and E-methylenecyclopropane nucleoside analogues were synthesized and 
      tested for antiviral activity in vitro against human and murine cytomegalovirus 
      (HCMV, MCMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), hepatitis B 
      virus (HBV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpesvirus 
      6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1). The 
      Z-2-amino-6-cyclopropylaminopurine analogue was the most effective agent against 
      HCMV (EC50 or EC90 0.4-2 microM) followed by syncytol and the Z-2,6-diaminopurine 
      analogues (EC50 or EC90 3.4-29 and 11-24 microM, respectively). The latter 
      compound was also a strong inhibitor of MCMV (EC50 0.6 microM). Syncytol was the 
      most potent against EBV (EC50 < 0.41 and 2.5 microM) followed by the 
      Z-2,6-diaminopurine (EC50 1.5 and 6.9 microM) and the 
      Z-2-amino-6-cyclopropyl-aminopurine derivative (EC50 11.8 microM). Syncytol was 
      also most effective against VZV (EC50 3.6 microM). Activity against HSV-1, HSV-2 
      and HHV-6 was generally lower; synthymol had an EC50 of 2 microM against HSV-1 
      (ELISA) and 1.3 microM against EBV in Daudi cells but was inactive in other 
      assays. The 2-amino-6-cyclopropylamino analogue displayed EC50 values between 215 
      and > 74 microM in HSV-1 and HSV-2 assays. 2-Amino-6-cyclopropylaminopurine and 
      2,6-diaminopurine derivatives were effective against HBV (EC50 2 and 10 microM, 
      respectively), whereas none of the analogues inhibited HIV-1 at a higher virus 
      load. Syncytol and the E isomer were equipotent against EBV in Daudi cells but 
      the E isomer was much less effective in DNA hybridization assays. The 
      E-2,6-diaminopurine analogue and E isomer of synthymol were devoid of antiviral 
      activity.
FAU - Qiu, Y L
AU  - Qiu YL
AD  - Department of Chemistry, Barbara Ann Karmanos Cancer Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201-1379, USA.
FAU - Ptak, R G
AU  - Ptak RG
FAU - Breitenbach, J M
AU  - Breitenbach JM
FAU - Lin, J S
AU  - Lin JS
FAU - Cheng, Y C
AU  - Cheng YC
FAU - Kern, E R
AU  - Kern ER
FAU - Drach, J C
AU  - Drach JC
FAU - Zemlicka, J
AU  - Zemlicka J
LA  - eng
GR  - R01-CA32779/CA/NCI NIH HHS/United States
GR  - R01-CA44358/CA/NCI NIH HHS/United States
GR  - U19-AI31718/AI/NIAID NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Antivir Chem Chemother
JT  - Antiviral chemistry & chemotherapy
JID - 9009212
RN  - 0 (Antiviral Agents)
RN  - 0 (Cyclopropanes)
RN  - 0 (Purines)
RN  - 0 (Pyrimidines)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*chemical synthesis/pharmacology
MH  - Cell Line
MH  - Cyclopropanes/*chemical synthesis/pharmacology
MH  - Cytomegalovirus/drug effects
MH  - HIV/drug effects
MH  - Hepatitis B virus/drug effects
MH  - Herpesvirus 3, Human/drug effects
MH  - Herpesvirus 4, Human/drug effects
MH  - Humans
MH  - Molecular Structure
MH  - Purines/*chemical synthesis
MH  - Pyrimidines/*chemical synthesis
MH  - Rats
MH  - Virus Replication/drug effects
EDAT- 1999/01/06 00:00
MHDA- 1999/01/06 00:01
CRDT- 1999/01/06 00:00
PHST- 1999/01/06 00:00 [pubmed]
PHST- 1999/01/06 00:01 [medline]
PHST- 1999/01/06 00:00 [entrez]
PST - ppublish
SO  - Antivir Chem Chemother. 1998 Jul;9(4):341-52.