Design and Discovery of α-Oximido-arylacetamides as Novel Antifungal Leads.

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 µM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 µM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation.

Discovery of zeylenone from Uvaria grandiflora as a potential botanical fungicide.

BACKGROUND: Botanical pesticides play an important role in organic agricultural practices and are widely used in integrated pest management (IPM). Uvaria grandiflora was mainly reported as traditional medicines and possessed antibacterial, antioxidant, and antiprotozoal activities. Therefore, important biological activities of U. grandiflora may suggest that they have the potential to be used as botanical pesticides. RESULTS: The extract of U. grandiflora exhibited broad-spectrum inhibitory activity toward phytopathogenic fungi and oomycetes, particularly against Colletotrichum musae and Phytophthora capsici, and its secondary metabolite zeylenone also displayed strong antifungal and anti-oomycete activities against phytopathogens. Particularly, half maximal effective concentration (EC50 ) values of zeylenone against Phytophthora capsici and C. musae were 6.98 and 3.37 µg mL-1 , showing better inhibitory effects than those of commercial fungicides (azoxystrobin and osthole). Additionally, the pot experiments showed that the extract of U. grandiflora could effectively control Pseudoperonospora cubensis, Phytophthora infestans, Phytophthora capsici and Podosphaera xanthii. In the field experiment, 5% microemulsion of U. grandiflora extract exhibited 79.72% efficacy against cucumber powdery mildew at 87.5 g ha-1 on the 14th day after two sprayings, which was better than that of 21.5% trifloxystrobin and 21.5% fluopyram SC at 200.9 g ha-1 . Surprisingly, 5% microemulsion of U. grandiflora extract could promote cucumber growth significantly. Furthermore, the action mechanism analysis indicated that zeylenone may damage the cytoderm and affect energy metabolism of Phytophthora capsici. CONCLUSION: It is the first time that the extract of U. grandiflora and zeylenone have been discovered leading to broad application prospects in the development as botanical fungicides. © 2021 Society of Chemical Industry.

Photostable 1-Trifluoromethyl Cinnamyl Alcohol Derivatives Designed as Potential Fungicides and Bactericides.

In the current work, a series of 1-trifluoromethyl cinnamyl alcohol derivatives were designed and synthesized and their antifungal activities were evaluated. The bioassay result showed that most compounds exhibited excellent antifungal activity in vitro at 10 µg mL-1. Next, photostable and easily synthesized compound 2 with broad-spectrum antifungal activity in vitro was selected as a potential candidate to evaluate its antibacterial and antifungal activities. The EC50 values of compound 2 against eight fungal plant pathogens in vitro ranged from 3.806 to 17.981 µg mL-1; at the same time, compound 2 could effectively control Podosphaera xanthii, Odium heveae Steinm, Puccinia striiformis West, and Puccinia sorghi in pot experiments. In addition, compound 2 exhibited excellent antibacterial activities in vitro and in vivo against Xanthomonas oryzae pv. oryzae. Furthermore, the absorption and translocation of compound 2 in wheat plants were determined by the high-performance liquid chromatography method. The result showed that compound 2 could be translocated acropetally as well as basipetally in wheat plants. Finally, it was found that compound 2 had no cross-resistance with carbendazim, azoxystrobin, and boscalid.

Discovery of N-Aryl-pyridine-4-ones as Novel Potential Agrochemical Fungicides and Bactericides.

A series of N-aryl-pyridine-4-one derivatives were designed and synthesized using maltol and antidesmone as lead compounds, and then their fungicidal/bactericidal activities and possible mechanism of action against Colletotrichum musae were explored. Most of these compounds exhibited significant fungicidal activity in vitro. Especially, compound 23 has more than 90% inhibitory activity against nine plant pathogenic fungi at 50 µg mL-1, which is superior to azoxystrobin. Moreover, an in vivo bioassay also demonstrated that compound 23 exhibited high-efficiency broad-spectrum antifungal activity and can effectively control postharvest diseases of mango. In addition, it was found that compounds 22 and 23 can also effectively control rice bacterial leaf blight in pot experiments, which was even more effective than zhongshengmycin. Preliminary mechanism studies revealed that compound 23 may cause cell membrane and mitochondria destruction. These findings indicate that compound 23 can be used to develop potential agrochemical fungicides and bactericides.