Title: Investigations on the anti-hiv activity of 2',3'-dideoxyadenosine analogs with modifications in either the pentose or purine moiety - potent and selective anti-hiv activity of 2,6-diaminopurine 2',3'-dideoxyriboside
Authors: Pauwels, R
Baba, M
Balzarini, Jan
Herdewijn, Piet
Desmyter, Jan
Robins, Mj
Zou, R
Madej, D
De Clercq, Erik #
Issue Date: Apr-1988
Publisher: Pergamon-elsevier science ltd
Series Title: Biochemical Pharmacology vol:37 issue:7 pages:1317-1325
Abstract: Several 2',3'-dideoxyadenosine analogues with modifications in either the ribose or purine moiety were evaluated for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in MT-4 cell cultures. The 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) inhibited HIV antigen expression and HIV-induced cytopathogenicity at a 50% effective dose of 2.4-3.8 microM, as compared to 3-6 microM for 2',3'-dideoxyadenosine (ddAdo), whereas 50% inhibition of MT-4 cell viability was noted only at a concentration of 477 and 889 microM, respectively. Both ddDAPR and ddAdo were only weakly inhibitory to the proliferation of a number of T-lymphoblast and T-lymphocyte cell lines, pointing to the selectivity of these compounds as anti-HIV agents. In contrast to ddAdo, ddDAPR was found to be a poor substrate for adenosine deaminase, which may be advantageous from a chemotherapeutic viewpoint. Substitution of an azido or fluoro group at the 2' and 3'-position of the ribose moiety in either "up" or "down" configurations resulted in a decrease of the anti-HIV potency and selectivity of ddAdo. In addition to ddDAPR other purine-modified ddAdo analogues, i.e. several pyrrolo[2,3-d]pyrimidine 2',3'-dideoxynucleosides, were investigated for their anti-HIV activity, but none of these derivatives proved as potent or selective as ddDAPR.
ISSN: 0006-2952
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Medicinal Chemistry (Rega Institute)
# (joint) last author

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