Combinatorial Synthesis of Indole Derivatives as Anti-oomycetes Agents

Fei Hai; Ruxue Wei; Yan Li; Ruiguang Wang; Yuee Tian; Shengming Liu; Genqiang Chen; Zhiping Che

doi:10.2174/0113862073252234231017062643

Combinatorial Synthesis of Indole Derivatives as Anti-oomycetes Agents

Comb Chem High Throughput Screen. 2023 Oct 27. doi: 10.2174/0113862073252234231017062643. Online ahead of print.

Authors

Fei Hai¹, Ruxue Wei², Yan Li², Ruiguang Wang², Yuee Tian², Shengming Liu², Genqiang Chen², Zhiping Che²

Affiliations

¹ Henan Vocational College of Agriculture College of Agricultural Engineering Henan China.
² Laboratory of Pesticidal Design & Synthesis, Department of Plant Protection, College of Horticulture and Plant Protection, Henan University of Science and Technology, Luoyang 471023, China.

PMID: 37929728
DOI: 10.2174/0113862073252234231017062643

Abstract

Background: Developing high-efficiency and low-risk small-molecule green fungicide is the key to effective control of the plant pathogenic oomycetes. Indole is an important raw material for drug synthesis. Due to its unique structural skeleton, indole, and its derivatives have exhibited a wide range of biological activities. However, a study on the synthesis of novel indole derivatives as fungicidal agents against Phytophthora capsici has not yet been reported.

Methods: The important intermediates 2a-c and 3a-c were synthesized in high yields by Vilsmeier- Haack and Knoevenagel reactions with indole as the lead compound. Furthermore, different substituted benzenesulfonyl groups were introduced into the NH position of the indole ring, and twelve indole derivatives (I-a-l) were prepared. Their structures were well characterized by 1H NMR, HRMS, and melting point.

Results: The results showed that 2-[(N-(4-nitrobenzenesulfonyl)-indole-3)-methylene]-diethyl malonate (I-d) and 2-[(N-(4-nitrobenzenesulfonyl)-5-cyanoindole-3)-methylene]-diethyl malonate (I-l) showed more anti-oomycete activity against P. capsici than the commercialized fungicide zoxamide, with corresponding EC50 values of 26.53, 23.48 and 28.16 mg/L, respectively, and the protective effect of the compounds against P. capsici in vivo further confirmed the above results.

Conclusion: The preliminary structure-activity relationship showed that the formyl group modification at the C-3 position of the indole ring was acceptable, and the different anti-oomycete activities of R1 and R2 were significantly different, with R1 being 5-CN > H > 6-Me, and R2 being 4-NO2 > 3-NO2, H > 4-Me.

Keywords: Natural product; Phytophthora capsici.; anti-oomycete activity; indole; synthesis.