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

摘要

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 S. 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.