PMID- 16127046
OWN - NLM
STAT- MEDLINE
DCOM- 20051122
LR  - 20191220
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 49
IP  - 9
DP  - 2005 Sep
TI  - Comparative activities of lipid esters of cidofovir and cyclic cidofovir against 
      replication of herpesviruses in vitro.
PG  - 3724-33
AB  - Cidofovir (CDV) is an effective therapy for certain human cytomegalovirus (HCMV) 
      infections in immunocompromised patients that are resistant to other antiviral 
      drugs, but the compound is not active orally. To improve oral bioavailability, a 
      series of lipid analogs of CDV and cyclic CDV (cCDV), including 
      hexadecyloxypropyl-CDV and -cCDV and octadecyloxyethyl-CDV and -cCDV, were 
      synthesized and found to have multiple-log-unit enhanced activity against HCMV in 
      vitro. On the basis of the activity observed with these analogs, additional lipid 
      esters were synthesized and evaluated for their activity against herpes simplex 
      virus (HSV) types 1 and 2, human cytomegalovirus, murine cytomegalovirus, 
      varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 
      (HHV-6), and HHV-8. Using several different in vitro assays, concentrations of 
      drug as low as 0.001 microM reduced herpesvirus replication by 50% (EC50) with 
      the CDV analogs, whereas the cCDV compounds were generally less active. In most 
      of the assays performed, the EC50 values of the lipid esters were at least 
      100-fold lower than the EC50 values for unmodified CDV or cCDV. The lipid analogs 
      were also active against isolates that were resistant to CDV, ganciclovir, or 
      foscarnet. These results indicate that the lipid ester analogs are considerably 
      more active than CDV itself against HSV, VZV, CMV, EBV, HHV-6, and HHV-8 in 
      vitro, suggesting that they may have potential for the treatment of infections 
      caused by a variety of herpesviruses.
FAU - Williams-Aziz, Stephanie L
AU  - Williams-Aziz SL
AD  - University of Alabama School of Medicine, 1600 6th Ave. South, 128 Children's 
      Harbor Bldg., Birmingham, AL 35233, USA.
FAU - Hartline, Caroll B
AU  - Hartline CB
FAU - Harden, Emma A
AU  - Harden EA
FAU - Daily, Shannon L
AU  - Daily SL
FAU - Prichard, Mark N
AU  - Prichard MN
FAU - Kushner, Nicole L
AU  - Kushner NL
FAU - Beadle, James R
AU  - Beadle JR
FAU - Wan, W Brad
AU  - Wan WB
FAU - Hostetler, Karl Y
AU  - Hostetler KY
FAU - Kern, Earl R
AU  - Kern ER
LA  - eng
GR  - N01AI30049/AI/NIAID NIH HHS/United States
GR  - EY11834/EY/NEI NIH HHS/United States
GR  - N01 AI30049/AI/NIAID NIH HHS/United States
GR  - N01 AI085347/AI/NIAID NIH HHS/United States
GR  - N01-AI-30049/AI/NIAID NIH HHS/United States
GR  - AI29164/AI/NIAID NIH HHS/United States
GR  - R37 AI029164/AI/NIAID NIH HHS/United States
GR  - N01-AI-85347/AI/NIAID NIH HHS/United States
GR  - R01 EY007366/EY/NEI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (Esters)
RN  - 0 (Organophosphonates)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 8J337D1HZY (Cytosine)
RN  - EUY85H477I (thiazolyl blue)
RN  - JIL713Q00N (Cidofovir)
SB  - IM
MH  - Antiviral Agents/chemistry/*pharmacology
MH  - Cell Adhesion/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cidofovir
MH  - Cyclization
MH  - Cytomegalovirus/drug effects
MH  - Cytosine/*analogs & derivatives/chemistry/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Esters/pharmacology
MH  - Fibroblasts/virology
MH  - Flow Cytometry
MH  - Herpesviridae/*drug effects
MH  - Humans
MH  - In Situ Hybridization
MH  - Organophosphonates/chemistry/*pharmacology
MH  - Structure-Activity Relationship
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Viral Plaque Assay
MH  - Virus Replication/*drug effects
PMC - PMC1195409
EDAT- 2005/08/30 09:00
MHDA- 2005/12/13 09:00
PMCR- 2005/09/01
CRDT- 2005/08/30 09:00
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
PHST- 2005/09/01 00:00 [pmc-release]
AID - 49/9/3724 [pii]
AID - 0291-05 [pii]
AID - 10.1128/AAC.49.9.3724-3733.2005 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2005 Sep;49(9):3724-33. doi: 
      10.1128/AAC.49.9.3724-3733.2005.