Small Changes Result in Large Differences: Discovery of (−)-Incrustoporin Derivatives as Novel Antiviral and Antifungal Agents

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.