A new potential aphicide against Myzus persicae: Design, synthesis and 3D-QSAR of novel phenoxypyridine derivatives containing 4-aminopyrimidine

Wang, Lizeng; Yang, Zhaokai; Pan, Shixiang; Zhu, Minna; Guan, Aiying; Sun, Xuemei; Zhang, Jinbo; Song, Yuquan; Liu, Changling; Yang, Xinling

doi:10.1016/j.molstruc.2022.132949

Cited by 9 publications

(3 citation statements)

References 16 publications

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“…Flufenerim has been previously developed as a pesticide against agricultural pests, including aphids ( Aphis medicaginis and Myzus persicae ), a fungus ( Pseudoperonospora cubensis ), moths ( Mythimna separata and Spodoptera littoralis ) and whiteflies ( Bemisia tabaci ) [ 68 – 70 ]. The mode of action of flufenerim is unclear.…”

Section: Discussionmentioning

confidence: 99%

A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity

Shanley,

Taki,

Byrne

et al. 2024

Parasites Vectors

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Background Infection with parasitic nematodes (helminths), particularly those of the order Strongylida (such as Haemonchus contortus), can cause significant and burdensome diseases in humans and animals. Widespread drug (anthelmintic) resistance in livestock parasites, the absence of vaccines against most of these nematodes, and a lack of new and effective chemical entities on the commercial market demands the discovery of new anthelmintics. In the present study, we searched the Global Health Priority Box (Medicines for Malaria Venture) for new candidates for anthelmintic development. Methods We employed a whole-organism, motility-based phenotypic screening assay to identify compounds from the Global Health Priority Box with activity against larvae of the model parasite H. contortus, and the free-living comparator nematode Caenorhabditis elegans. Hit compounds were further validated via dose–response assays, with lead candidates then assessed for nematocidal activity against H. contortus adult worms, and additionally, for cytotoxic and mitotoxic effects on human hepatoma (HepG2) cells. Results The primary screen against H. contortus and C. elegans revealed or reidentified 16 hit compounds; further validation established MMV1794206, otherwise known as ‘flufenerim’, as a significant inhibitor of H. contortus larval motility (half-maximal inhibitory concentration [IC50] = 18 μM) and development (IC50 = 1.2 μM), H. contortus adult female motility (100% after 12 h of incubation) and C. elegans larval motility (IC50 = 0.22 μM). Further testing on a mammalian cell line (human hepatoma HepG2 cells), however, identified flufenerim to be both cytotoxic (half-maximal cytotoxic concentration [CC50] < 0.7 μM) and mitotoxic (half-maximal mitotoxic concentration [MC50] < 0.7 μM). Conclusions The in vitro efficacy of MMV1794206 against the most pathogenic stages of H. contortus, as well as the free-living C. elegans, suggests the potential for development as a broad-spectrum anthelmintic compound; however, the high toxicity towards mammalian cells presents a significant hindrance. Further work should seek to establish the protein–drug interactions of MMV1794206 in a nematode model, to unravel the mechanism of action, in addition to an advanced structure–activity relationship investigation to optimise anthelmintic activity and eliminate mammalian cell toxicity. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity

Shanley,

Taki,

Byrne

et al. 2024

Parasites Vectors

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“…Some insecticides and acaricides (flufenerim, purimidifen, tebufenpyrad, and tolfenpyrad [ 103 ]) worked by inhibiting the mitochondrial electron transport (MET) at complex I to disrupt respiration, known as complex I inhibitors [ 104 ]. Most of the 4-aminopyrimidine [ 105 ] derivatives that were synthesized by Wang et al [ 106 ] through intermediate derivatization methods showed good activity against Myzus persicae , among which 56 ( Figure 12 ) had the highest activity and the lowest LC 50 value of 0.34 mg/L.…”

Section: Insecticides Containing Phenoxypyridine Scaffoldmentioning

confidence: 99%

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Liu

Yong

et al. 2022

Molecules

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Phenoxypyridine, the bioisostere of diaryl ethers, has been widely introduced into bioactive molecules as an active scaffold, which has different properties from diaryl ethers. In this paper, the bioactivities, structure-activity relationships, and mechanism of compounds containing phenoxypyridine were summarized, which may help to explore the lead compounds and discover novel pesticides with potential bioactivities.

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“…For example, Fenclorim ( II ) is a herbicide used for controlling annual grasses, broadleaf weeds, and some edges − (Figure ). On the other hand, Heythiazox ( III ) belongs to a thiazolidinone derivative having nymphicidal and larvicidal potential toward mites and leafhoppers that could be administrated at any plant growth stage from budding till fruiting (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Green Design, Synthesis, and Molecular Docking Study of Novel Quinoxaline Derivatives with Insecticidal Potential against Aphis craccivora

et al. 2022

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An efficient and environmentally friendly method was established for designing novel 3-amino-1,4-dihydroquinoxaline-2-carbonitrile ( 1 ) via the reaction of bromomalononitrile and benzene-1,2-diamine under microwave irradiation in an excellent yield (93%). This targeted amino derivative was utilized for the construction of a series of Schiff bases ( 8 – 13 ). A new series of thiazolidinone derivatives ( 15 – 20 ) were synthesized in high yields (89–96%) via treatment of thioglycolic acid with Schiff bases ( 8 – 13 ) under microwave irradiation in high yields (89–96%). Moreover, new pyrimidine derivatives ( 26 – 30 and 35 – 38 ) were prepared by treatment of compound 1 with arylidenes ( 21 – 25 ) and/or alkylidenemalononitriles ( 31 – 34 ) using piperidine as a basic catalyst under microwave conditions. Based on elemental analyses and spectral data, the structures of the new assembled compounds were determined. The newly synthesized quinoxaline derivatives were screened and studied as an insecticidal agent against Aphis craccivora . The obtained results indicate that compound 16 is the most toxicological agent against nymphs of cowpea aphids ( Aphis craccivora ) compared to the other synthesized pyrimidine and thiazolidinone derivatives. The molecular docking study of the new quinoxaline derivatives registered that compound 16 had the highest binding score (−10.54 kcal/mol) and the thiazolidinone moiety formed hydrogen bonds with Trp143.

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A new potential aphicide against Myzus persicae: Design, synthesis and 3D-QSAR of novel phenoxypyridine derivatives containing 4-aminopyrimidine

Cited by 9 publications

References 16 publications

A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity

A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Green Design, Synthesis, and Molecular Docking Study of Novel Quinoxaline Derivatives with Insecticidal Potential against Aphis craccivora

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