title: In vitro and in vivo antiherpetic effects of (1R,2R)-1-(5'-methylful-3'-yl)propane-1,2,3-triol.
abstract: In this study, we demonstrated the in vitro and in vivo antiherpetic activities of a stable furan derivative, (1R,2R)-1-(5'-methylful-3'-yl)propane-1,2,3-triol (MFPT), which had originally been isolated from Streptomyces sp. strain FV60. In the present study, we synthesized MFPT from (5-methylfuran-3-yl)methanol in 6 steps for use in the experiments. MFPT showed potent in vitro antiviral activities against two acyclovir (ACV)-sensitive (KOS and HF) strains and an ACV-resistant (A4-3) strain of herpes simplex virus type 1 (HSV-1) and an ACV-sensitive HSV type 2 (HSV-2) UW 268 strain, their selectivity indices ranging from 310 to 530. By intravaginal application of MFPT to mice, the virus yields decreased dose-dependently against the three strains of HSV-1 and HSV-2. When MFPT was applied at a dose of 1.0 mg/day, the lesion scores, as clinical signs manifested by viral infection, were extensively suppressed in HSV-1-infected mice, whereas the lesion scores in HSV-2-infected mice were not markedly decreased. Interestingly, MFPT exerted an inhibitory effect against ACV-resistant HSV-1 in mice to a similar degree as in ACV-sensitive HSV-1-infected mice. Therefore, the compound might have potential for developing a topical antiviral agent that could be also applied to the infections caused by ACV-resistant viruses.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Research Institute of Life and Health Sciences, Chubu University, Kasugai, Aichi, 487-8501, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuya
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan. lee@pha.u-toyama.ac.jp.
authors.forename: Jung-Bum
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Kurosaki
authors.affiliation: Research Institute of Life and Health Sciences, Chubu University, Kasugai, Aichi, 487-8501, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use; D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D004351:Drug Resistance; D005260:Female; D005663:Furans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D006558:Herpes Genitalis / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D011407:Propane; D013302:Streptomyces / Q000737:chemistry; D014709:Vero Cells
chemical_list: C000611404:(1R,2R)-1-(5'-methylful-3'-yl)propane-1,2,3-triol; D000998:Antiviral Agents; D005663:Furans; D005990:Glycerol; D011407:Propane; C039281:furan; D000212:Acyclovir
keywords: (1R,2R)-1-(5′-methylful-3′-yl)propane-1,2,3-triol (MFPT); Antiherpetic activity; Herpes simplex virus type 1; Herpes simplex virus type 2; Intravaginal application