title: Small changes result in large differences: discovery of (-)-incrustoporin derivatives as novel antiviral and antifungal agents.
abstract: On the basis of the structure of natural product (-)-incrustoporin (1), a series of lactone compounds 4a-i and 5a-i were designed and synthesized from nitroolefin. The antiviral and antifungal activities of these compounds were evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4-position result in large differences in bioactivities. Compounds 4 exhibited significantly higher antiviral activity against tobacco mosaic virus (TMV) than dehydro compounds 5. However, the antifungal activity of 4 is relatively lower than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity emerged as new antiviral lead compounds. Compounds 5d-g showed superiority over the commercial fungicides chlorothalonil and carbendazim against Cercospora arachidicola Hor at 50 mg kg(-1). The present study provides fundamental support for the development and optimization of (-)-incrustoporin derivatives as potential inhibitors of plant virus and pathogenic fungi.
authors.affiliation: School of Marine Science and Engineering and ‡School of Chemical Engineering, Hebei University of Technology , Tianjin 300130, China.
authors.forename: Aidang
authors.initials: A
authors.lastname: Lu
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wang
authors.forename: Tengjiao
authors.initials: T
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D005659:Fungicides, Industrial / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D000998:Antiviral Agents; D005659:Fungicides, Industrial; C094022:incrustoporin; D015107:4-Butyrolactone