2-Arylindoles: Concise Syntheses and a Privileged Scaffold for Fungicide Discovery

Abstract

Indole is a popular and functional scaffold existing widely in the fields of medicine, pesticides, spices, food and feed additives, dyes, and many others. Among indoles, 2-arylindole represents a particular and interesting subset but has attracted less attention for drug discovery. In this study, we report a general, practical one-pot assembly of a variety of 2-arylindole derivatives. To develop novel fungicide scaffolds, their fungicide activity was also evaluated. The bioassay results showed that many of the synthesized 2-arylindoles exhibited considerable fungicidal activities especially toward <i>Rhizoctonia cerealis</i>, and several demonstrated an inhibition rate of more than 90%. Notably, 4-fluoro-2-phenyl-1<i>H</i>-indole <b>6e</b> was obtained with a broad spectrum of fungicidal activities, which showed excellent growth inhibition activities against <i>R. cerealis</i>, <i>Rhizoctonia solani</i>, <i>Botrytis cinerea</i>, <i>Magnaporthe oryza</i>, and <i>Sclerotinia sclerotiorum</i> with EC₅₀ values of 2.31, 4.98, 6.78, 10.57, and 17.80 μg/mL, respectively. Preliminary fungicidal mode of action of <b>6e</b> showed a significant inhibition effect on mycelial growth and spore germination. These results indicated that 2-arylindoles as privileged scaffolds exhibited potential fungicidal activities that deserve further study.