title: Design and SAR of new substituted purines bearing aryl groups at N9 position as HIV-1 Tat-TAR interaction inhibitors.
abstract: Twenty-four purine derivatives bearing aryl groups at N9 position were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Ten of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells at a concentration of 30 microM, indicating effective inhibitory activities of blocking the Tat-TAR interaction. The aryl groups at N9 position affected the binding affinities between compounds and TAR RNA, showing some specificities of aryl groups to TAR RNA.
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, PO Box 261, Beijing 100083, PR China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Pang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.forename: Dekai
authors.initials: D
authors.lastname: Yuan
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA / Q000187:drug effects / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D011687:Purines; D012313:RNA