In silico identification of the protein targets of chaetoglobosins and benzotriazines for the selection of alternative nematicides to control Meloidogyne incognita

Abstract

Phytonematodes of the genus Meloidogyne are parasites responsible for reducing agricultural production worldwide. Among the methods for controlling these parasites is chemical management, which can lead to contamination of humans and the environment with highly toxic substances. Therefore, new methods and products for controlling these nematodes, with less impact on humans and the environment, are in demand by society in general. As a result, several organic substances active against nematodes have been identified. However, the production of these substances on a commercial scale is not always feasible, which makes it necessary to use them as a basis for the development of new, affordable nematicides. To this end, computational chemistry is a very promising tool. Therefore, in order to contribute to the development of new nematicides for the control of Meloidogyne spp., this work aimed to identify in silico the protein targets of chaetoglobosins A and B, and benzotriazines A6 and A8, in the aforementioned nematodes, so that they can serve as models for the future generation of more efficient chemical structures as nematicides. In addition, the ematicidal activities of the inhibitors of the targets of each group of substances were also investigated in vitro and in vivo. The results of the in silico study show that the affinities of chaetoglobosins A and B for the sodium-dependent serotonin transporter protein (SERT) are similar to the affinities calculated for inhibitors of this protein; and that the affinities of benzoatriazines A6 and A8 for mitogen-activated protein kinase 14 (MAPK14) are also similar to the values calculated for inhibitors of this protein. Among the SERT inhibitors, paroxetine was selected, which showed a lethal concentration for 50% (LC 50 ) of Meloidogyne incognita second stage juveniles (J2) equal to 351.26 μg/mL. Under the same conditions, the positive control (fluensulfone) showed an LC50 of 39.31 μg/mL. Paroxetine also reduced the pathogenicity of M. incognita under greenhouse conditions. Among the MAPK14 inhibitors, the most promising was TCS ERK 11e, which showed moderate nematicidal activity against J2 of M. incognita in vitro. Therefore, the future study of SERT and MAPK14 inhibitors is potentially useful for the development of new nematicides to control M. incognita .