Design, Synthesis, and Biological Activity Evaluation of 5-Aryl-cyclopenta[]pyridine Derivatives.

Taking the natural product cerbinal as the lead compound, 30 novel 5-aryl-cyclopenta[]pyridine derivatives were designed and synthesized based on the previous bioactivity studies of the cyclopenta[]pyridines. The modification of the position-5 of compound was achieved by amination, bromination, and cross coupling using cerbinal as the raw material. The results of the bioactivity tests demonstrated that partial compounds exhibited superior activity against plant viruses compared to compound . Compounds and showed higher anti-TMV activity levels than commercial varieties of ribavirin at concentrations of 500 and 100 μg/mL. In particular, compound , which contained a -methoxyphenyl substitution, displayed the most potent anti-TMV activity (inactivation effect 51.1 ± 1.9%, curative effect 50.7 ± 3.6%, protection effect 53.8 ± 2.8% at 500 μg/mL) The toxicological experiments also revealed that compound exhibited low toxicity to zebrafish. Additionally, molecular docking results indicated that access to the benzene ring enhanced the binding affinity of these derivatives for TMV receptor proteins. Furthermore, studies on the insecticidal and fungicidal activities of these derivatives showed that most of the compounds exhibited good larvicidal efficacy against and broad-spectrum fungicidal activities. Notably, compound (3,4,5-trifluorophenyl) displayed an outstanding inhibition ratio of 91.9% against , 75% against , and 62.5% against at a concentration of 50 μg/mL. These results suggest that 5-aryl-cyclopenta[]pyridine derivatives could serve as promising candidate agents for antiviral, insecticidal, and fungicidal applications in agricultural production.