{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu R"],"funding":["NIAID NIH HHS"],"pagination":["7958-66"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2990348"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["53(22)"],"pubmed_abstract":["Bioisosteric deaza analogues of 6-methyl-9-?-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-?-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC(50) = 11 nM) and dengue virus (DENV) in Vero cells (IC(50) = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-?-D-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP."],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses."],"pmcid":["PMC2990348"],"funding_grant_id":["AI054776","U01 AI054776","U01 AI082068-01","U01 AI054776-05","R01 AI070791","R01 AI045818","AI070791","AI082068","U01 AI082068","R01 AI070791-01"],"pubmed_authors":["Cameron CE","Padmanabhan R","Peterson BR","Wu R","Smidansky ED","Oh HS","Takhampunya R"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses.","description":"Bioisosteric deaza analogues of 6-methyl-9-?-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-?-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC(50) = 11 nM) and dengue virus (DENV) in Vero cells (IC(50) = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-?-D-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Nov","modification":"2020-10-31T08:20:47Z","creation":"2019-03-27T00:36:50Z"},"accession":"S-EPMC2990348","cross_references":{"pubmed":["20964406"],"doi":["10.1021/jm100593s"]}}