Design, synthesis and antimicrobial activity evaluation of novel tetrahydrocarbazole derivatives against phytopathogenic fungi and bacteria.

Abstract

Plant pathogenic bacteria and fungi had a wide impact on various crops and caused serious economic losses. Compared to traditional antibiotics and fungicides, alkaloids are noteworthy for their significant biological activities. Tetrahydrocarbazole (THCz) was widely present in many indole alkaloids and had various pharmacological activities. This study used Fischer indole synthesis method and fragment splicing strategy to design and synthesize a novel drug like chemical entity based on THCz alkaloid guidance, evaluated the antimicrobial activities of these derivatives against plant pathogenic bacteria and fungi and discussed the structure-activity relationship. Among these derivatives, compound KZa-17 displayed good antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri, Pseudo-monas sollamacearum and Erwinia aroideae. The MIC90 values were 3.12, 1.56, 6.25, 12.5 μg/mL, respectively, which were better than the positive control drugs thiodiazole copper and bismerthiazol. The results of in vivo antibacterial activity test showed that the protective effect of compound KZa-17 on rice at 200 μg/mL was 32.76%, which was better than that of thiodiazole copper (24.73%). The biochemical experiments showed that compound KZa-17 could inhibit biofilm formation of Xoo, reduce drug resistance and pathogenicity of bacteria, damage cell membrane integrity, increase permeability, and cause oxidative stress damage. Most of the newly synthesized derivatives based on THCz alkaloid guidance showed favorable antimicrobial effects. In particular, compound KZa-17 can be used as a candidate lead compound for further structural optimization and development. © 2024 Society of Chemical Industry.