title: Design, synthesis and biological evaluation of substituted guanidine indole derivatives as potential inhibitors of HIV-1 Tat-TAR interaction.
abstract: The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Rujun
authors.initials: R
authors.lastname: Bai
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Key Laboratory of Chemical Biology (Educational Ministry of China) and Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China. xinyongl@sdu.edu.cn.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D019791:Guanidine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D007211:Indoles; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D019791:Guanidine