5-Fluoro-4-iodo-1H-pyrrolo(2,3-b)pyridine

Many species of Paecilomyces are entomogenous fungi and several are efficacious toward nematodes. To study the potential of Paecilomyces species in controlling nematodes, fungal extracts of 40 Paecilomyces spp. were evaluated for their nematicidal activity against Bursaphelenchus xylophilus and Panagrellus redivivus. The extracts of six Paecilomyces spp. exhibited the nematicidal activity against P. redivivus, and 11 species exhibited the nematicidal activity against B. xylophilus. The methanol extract of strain 1.01761 incubating on Czapek solid medium killed more than 95% P. redivivus in 24 h at 5 mg/ml, and the filtrate of strain 1.01788 cultured in Sabouraud's broth medium resulted in 90% mortality of B. xylophilus in 24 h at 5 mg/ml. A novel nematicidal compound 4-(4'-carboxy-2'-ethyl-hydroxypentyl)-5,6-dihydro-6-methylcyclobuta[b]pyridine-3,6-dicarboxylic acid, was isolated from Paecilomyces sp. YMF1.01761. The LD(50) value of the compound within 24 h against P. redivivus was 50.86 mg/L, against Meloidogyne incognita was 47.1 mg/L, and against B. xylophilus was 167.7 mg/L.

Multi-drug resistance in nematodes is a serious problem as lately several resistant phenotypes have emerged following the intermittent usage of synthetic nematicides. Contemporary research continues to focus on developing and/or repurposing small molecule inhibitors that are eco-friendly. Here, we describe the repurposing of the indole derivative, 5-iodoindole, as a nematicide for the root-knot nematode, Meloidogyne incognita. 5-Iodoindole effectively killed juveniles and freshly hatched juveniles by inducing multiple vacuole formation. Notably, at higher dosage (50 μg/mL), 5-iodoindole induced rapid juvenile death within 6 h. Microscopic analysis confirmed that the rapid death was due to the generation of reactive oxygen species (ROS). Computational docking attributed this ROS production to the antagonistic effect of 5-iodoindole on glutathione S-transferase (GST), which is known to play a critical role in the suppression of ROS in nematode models. Furthermore, 5-iodoindole also effectively reduced the gall formations and eggs masses of M. incognita on Solanum lycopersicum roots in pot experiments, and importantly it did not harm the physiological properties of the plant. Overall, the study provides valuable insights on the use of 5-iodoindole as an alternate measure to control root-knot nematodes. Overall, our findings suggest the efficacy of 5-iodoindole should be studied under field conditions.

Bursaphelenchus xylophilus is a quarantined migratory endoparasite known to cause severe economic losses in pine forest ecosystems. The study presents the nematicidal effects of halogenated indoles on B. xylophilus and their action mechanisms. 5-Iodoindole and abamectin (positive control) at low concentration (10 µg/mL) presented similar and high nematicidal activities against B. xylophilus. 5-Iodoindole diminished fecundity, reproductive activities, embryonic and juvenile lethality and locomotor behaviors. Molecular interactions of ligands with invertebrate-specific glutamate gated chloride channel receptor reinforced the notion that 5-iodoindole, like abamectin, rigidly binds to the active sites of the receptor. 5-Iodoindole also induced diverse phenotypic deformities in nematodes including abnormal organ disruption/shrinkage and increased vacuolization. These findings suggest the prospective role of vacuoles in nematode death by methuosis. Importantly, 5-iodoindole was nontoxic to two plants, Brassica oleracea and Raphanus raphanistrum. Henceforth, the study warrants the application of iodoindoles in ecological environments to control the devastating pine destruction by B. xylophilus.