Design, Synthesis, and Antifungal Evaluation of Cryptolepine Derivatives against Phytopathogenic Fungi

Abstract

Inspired by the widely antiphytopathogenic application of diversified derivatives from natural sources, cryptolepine and its derivatives were subsequently designed, synthesized, and evaluated for their antifungal activities against four agriculturally important fungi <i>Rhizoctonia solani</i>, <i>Botrytis cinerea</i>, <i>Fusarium graminearum</i>, and <i>Sclerotinia sclerotiorum</i>. The results obtained from <i>in vitro</i> assay indicated that compounds <b>a1-a24</b> showed great fungicidal property against <i>B. cinerea</i> (EC₅₀ < 4 μg/mL); especially, <b>a3</b> presented significantly prominent inhibitory activity with an EC₅₀ of 0.027 μg/mL. In the pursuit of further expanding the antifungal spectrum of cryptolepine, ring-opened compound <b>f1</b> produced better activity with an EC₅₀ of 3.632 μg/mL against <i>R. solani</i> and an EC₅₀ of 5.599 μg/mL against <i>F. graminearum</i>. Furthermore, <b>a3</b> was selected to be a candidate to investigate its preliminary antifungal mechanism to <i>B. cinerea</i>, revealing that not only spore germination was effectively inhibited and the normal physiological structure of mycelium was severely undermined but also detrimental reactive oxygen was obviously accumulated and the normal function of the nucleus was fairly disordered. Besides, <i>in vivo</i> curative experiment against <i>B. cinerea</i> found that the therapeutic action of <b>a3</b> was comparable to that of the positive control azoxystrobin. These results suggested that compound <b>a3</b> could be regarded as a novel and promising agent against <i>B. cinerea</i> for its valuable potency.