title: Novel antiviral agent tetraglycylated nordihydroguaiaretic acid hydrochloride as a host-dependent viral inhibitor.
abstract: A water soluble derivative of nordihydroguaiaretic acid (NDGA), G(4)N (2), synthesized by reaction of NDGA (1) with N,N-dimethylglycine in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine and then with HCl(g) (Scheme 1), competes effectively with the DNA binding domain of recombinant Sp1 protein for binding to the human immunodeficiency virus (HIV) LTR as demonstrated by an electrophoretic mobility-shift assay (EMSA). By blocking Sp1 binding to the HIV LTR, G(4)N suppresses Sp1-regulated HIV Tat transactivation and replication in cultured cells with an IC(50) of 12 microM similar to that of 3'-O-methyl-NDGA as we have previously reported. In addition simian immunodeficiency virus (SIV) replication was completely inhibited by G(4)N at 5.0 microM. G(4)N showed no toxic effect to 174 x CEM cells and H9 cells at 100 microM.
authors.affiliation: Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA. RHUANG@JHU.EDU
authors.forename: Ru Chih C
authors.initials: RC
authors.lastname: Huang
authors.forename: Yen
authors.initials: Y
authors.lastname: Li
authors.forename: Paul E
authors.initials: PE
authors.lastname: Giza
authors.forename: John N
authors.initials: JN
authors.lastname: Gnabre
authors.forename: Ibrahim S
authors.initials: IS
authors.lastname: Abd-Elazem
authors.forename: Ke Yung
authors.initials: KY
authors.lastname: King
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D015696:Gene Products, tat / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009637:Masoprocol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D016329:Sp1 Transcription Factor; D054322:tat Gene Products, Human Immunodeficiency Virus; D009637:Masoprocol