Synthesis and antiviral activity of 2'-substituted 9-[2-(phosphonomethoxy)ethyl]guanine analogues

Details

Serval ID
serval:BIB_95A5FD225858
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synthesis and antiviral activity of 2'-substituted 9-[2-(phosphonomethoxy)ethyl]guanine analogues
Journal
Journal of Medicinal Chemistry
Author(s)
Yu  K. L., Bronson  J. J., Yang  H., Patick  A., Alam  M., Brankovan  V., Datema  R., Hitchcock  M. J., Martin  J. C.
ISSN
0022-2623
Publication state
Published
Issued date
09/1993
Peer-reviewed
Oui
Volume
36
Number
19
Pages
2726-38
Notes
Journal Article --- Old month value: Sep 17
Abstract
A series of 2'-substituted derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and evaluated in vitro for anti-human immunodeficiency virus (HIV) activity in the XTT assay and for anti-herpes activity in the plaque reduction assay. It has been observed that the anti-HIV activity of these derivatives depends on the size and the nature of the substituent as well as the chirality at the 2'-position of PMEG. In addition, these compounds generally demonstrated greater activity against HIV than herpes viruses. The most interesting analogues which emerged from these studies are (R)-2'-(azidomethyl)-PMEG [(R)-5] and (R)-2'-vinyl-PMEG [(R)-11]. The former showed anti-HIV activity with an IC50 of 5 microM and a cytotoxicity (CC50) greater than 1.4 mM in CEM cells. The latter has an IC50 of 13 microM for anti-HIV activity and a CC50 of greater than 1.6 mM. Furthermore, we have demonstrated that replacement of the guanine base of these 2'-substituted PMEG analogues with cytosine drastically reduces anti-HIV and anti-herpes activity.
Keywords
Antineoplastic Agents/pharmacology Antiviral Agents/*chemical synthesis/pharmacology Guanine/*analogs & derivatives/pharmacology Microbial Sensitivity Tests Organophosphorus Compounds/*chemical synthesis/pharmacology Structure-Activity Relationship
Pubmed
Web of science
Create date
20/01/2008 18:22
Last modification date
20/08/2019 14:57
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