title: Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues.
abstract: Lamellarin α and six different types of lamellarin α 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10 μM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin α and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC(50)>100 μM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication.
authors.affiliation: Graduate School of Science and Technology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Kamiyama
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kubo
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Fumito
authors.initials: F
authors.lastname: Ishibashi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Iwao
mesh_terms: D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D003374:Coumarins; D019428:HIV Integrase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C119474:lamellarin alpha 20-sulfate