TAILIEUCHUNG - Báo cáo khoa học: Anti-HIV-1 activity of 3-deaza-adenosine analogs Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners

Eight adenosine analogs, 3-deaza-adenosine (DZA), 3-deaza-(±)aristeromycin (DZAri), 2¢,3¢-dideoxy-adenosine (ddAdo), 2¢,3¢-dideoxy-3-deaza-adenosine (ddDZA), 2¢,3¢-dideoxy-3-deaza-(±)aristeromycin (ddDZAri), 3-deaza-5¢-(±)noraristeromycin (DZNAri), 3-deaza-neplanocin A (DZNep), and neplanocin A (NepA), were tested as inhibi-tors of human placentaS-adenosylhomocysteine (AdoHcy) hydrolase. The order of potency for the inhibition of human placental AdoHcy hydrolase was: DZNep NepA DZAri DZNAri DZA ddAdo ddDZA ddDZAri | Eur. J. Biochem. 270 3507-3517 2003 FEBS 2003 doi Anti-HIV-1 activity of 3-deaza-adenosine analogs Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners Richard K. Gordon1 Krzysztof Ginalski2 Witold R. Rudnicki3 Leszek Rychlewski4 Marvin C. Pankaskie5 Janusz M. Bujnicki6 and Peter K. Chiang1 1 Walter Reed Army Institute of Research Washington USA 2University of Texas Southwestern Medical Center Dallas USA 3Interdisciplinary Centre for Mathematical and Computational Modelling Warsaw University Poland 4BioInfoBank Institute Poznan Poland 5School of Pharmacy Palm Beach Atlantic University West Palm Beach Florida USA 6 Bioinformatics Laboratory International Institute of Molecular and Cell Biology Warsaw Poland Eight adenosine analogs 3-deaza-adenosine DZA 3-deaza- aristeromycin DZAri 2 3 -dideoxy-adenosine ddAdo 2 3 -dideoxy-3-deaza-adenosine ddDZA 2 3 -dideoxy-3-deaza- aristeromycin ddDZAri 3-deaza-5 - noraristeromycin DZNAri 3-deaza-neplanocin A DZNep and neplanocin A NepA were tested as inhibitors of human placenta S-adenosylhomocysteine AdoHcy hydrolase. The order of potency for the inhibition of human placental AdoHcy hydrolase was DZNep w NepA DZAri DzNah DZA ddAdo ddDZA w ddDZAri. These same analogs were examined for their anti-HIV-1 activities measured by the reduction in p24 antigen produced by 3 -azido-3 -deoxythymidine AZT -sensitive HIV-1 isolates A012 and A018 in phytohemagglutinin-stimulated peripheral blood mononuclear PBMCs cells. Interestingly DZNAri and the 2 3 -dideoxy 3-deaza-nucleosides ddAdo ddDZAri and ddDZA were only marginal inhibitors of p24 antigen production in HIV-1 infected PBMC. DZNAri is unique because it is the only DZA analog with a deleted methylene group that precludes anabolic phosphorylation. In contrast the other analogs were potent inhibitors of p24 antigen production by both HIV-1 isolates. Thus it was postulated that these nucleoside analogs could exert their antiviral effect

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