Novel Flavonol Derivatives Containing 1,3,4-Thiadiazole as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation

Abstract

In order to discover novel compounds with excellent agricultural activities, novel flavonol derivatives containing 1,3,4-thiadiazole were synthesized and evaluated for their antifungal activities. The bioassay results showed that some of the target compounds had good antifungal activities against <i>Botrytis cinerea</i>, <i>Phomopsis</i> sp. and <i>Sclerotinia sclerotiorum</i> in vitro. It is worth noting that the half-effective concentration (EC₅₀) value of <b>Y18</b> against <i>B. cinerea</i> was 2.4 μg/mL, which was obviously superior to that of azoxystrobin (21.7 μg/mL). The curative activity of <b>Y18</b> at 200 μg/mL (79.9%) was better than that of azoxystrobin (59.1%), and its protective activity (90.9%) was better than that of azoxystrobin (83.9%). Morphological studies by using scanning electron microscopy and fluorescence microscopy revealed that <b>Y18</b> could affect the normal growth of <i>B. cinerea</i> mycelium. In addition, the mechanism of action studies indicated that <b>Y18</b> could affect the integrity of cell membranes by inducing the production of endogenous reactive oxygen species and the release of the malondialdehyde content, leading to membrane lipid peroxidation and the release of cell contents. The inhibitory activity of flavonol derivatives containing 1,3,4-thiadiazole on plant fungi is notable, offering significant potential for the development of new antifungal agents.