title: [Anti-HIV-1 activity and structure-activity relationship of pyranocoumarin analogs].
abstract: The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 micromol x L(-1) of IC50 against HIV-1 PR/RT and 0.036 micromol x L(-1) against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Dong
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Pei-Zhen
authors.initials: PZ
authors.lastname: Tao
authors.forename: Xing-Quan
authors.initials: XQ
authors.lastname: Zhang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D039681:Pyranocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D039681:Pyranocoumarins; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1