Yuqin Ou, Xue Guo, Qi Zhang, Wei Zhang, Xiuhai Gan
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引用次数: 0
Abstract
Plant-parasitic nematodes are seriously affecting agricultural production worldwide and there are few highly effective and low-risk nematicides to control nematode diseases. In order to discover new nematicides, a series of 1,2,4-oxadiazole derivatives containing amide fragments have been designed and synthesized with the principle of active substructure splicing. The nematicidal activity of the target compounds was evaluated in vitro and it indicated that compound C3 exhibited the most nematicidal activity against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus destructor with the LC50 values of 37.2, 36.6, and 43.4 μg/mL, respectively, which were superior to positive agent tioxazafen. The preliminary mechanism results revealed that compound C3 not only inhibited the reproduction of B. xylophilus populations, but also affected the production of ROS and the accumulation of lipofuscin and lipids. Furthermore, compound C3 showed good inhibition of succinate dehydrogenase (SDH) with the IC50 value of 45.5 µmol/L. Molecular docking indicated that compound C3 had excellent binding to amino acids around the SDH active pocket. This work indicated that 1,2,4-oxadiazole derivative containing amide fragment is a promising template for the discovery of new nematicides and compound C3 can be used as a potential nematicide candidate.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;