title: The design, synthesis, and biological evaluation of novel substituted purines as HIV-1 Tat-TAR inhibitors.
abstract: A series of novel substituted purines containing a side chain with a terminal amino or guanidyl group were designed and synthesized as HIV-1 Tat-TAR inhibitors. All the compounds could effectively block the TAR transactivation in human 293T cells with the CAT expression percentage ranging from 34.4% to 65.7% and showed high antiviral effects with low cytotoxicities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Molecular modeling studies by Auto-dock process suggest that the compounds bind to TAR RNA in two different modes.
authors.affiliation: National Research Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100083, PR China.
authors.forename: Dekai
authors.initials: D
authors.lastname: Yuan
authors.forename: Meizi
authors.initials: M
authors.lastname: He
authors.forename: Ruifang
authors.initials: R
authors.lastname: Pang
authors.forename: Shrong-Shi
authors.initials: SS
authors.lastname: Lin
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D015726:Giant Cells / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D011687:Purines