Current Topics of the Inhibitors of Mitochondrial Complex I

Miyoshi, Hideto

doi:10.1007/978-94-007-4138-6_4

Cited by 3 publications

(2 citation statements)

References 76 publications

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“…Several natural and synthetic insecticides ( 50 – 53 ) inhibit mitochondrial respiration at Complex I or NADH:ubiquinone oxidoreductase (NADH oxidase) (Table ). The natural products are rotenone ( 50A ) and piericidin A ( 51 ), and the synthetics include pyridaben ( 52A ) and fenazaquin ( 53A ). In perhaps the first radioligand binding study with an insecticide, [ 14 C] 50A was shown to undergo specific and saturable binding in electron transport particles with an SAR consistent with its respiratory and toxic effects. − The assay was improved with [ 3 H]dihydrorotenone ( 50B ) in studies of Parkinson’s disease and the binding site localized in the substantia nigra .…”

Section: Various Targetsmentioning

confidence: 99%

Radioligand Recognition of Insecticide Targets

Casida

2018

J. Agric. Food Chem.

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Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH ubiquinone oxidoreductase. Pyrethroids and other Na channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

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Section: Various Targetsmentioning

confidence: 99%

Radioligand Recognition of Insecticide Targets

Casida

2018

J. Agric. Food Chem.

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“…The chiral γ-butenolactone moiety is a common pharmacophore of acetogenins. Bioenergetic production has been reported to be hindered by the inhibition of mitochondrial complex I. ,, In fact, 1 displays remarkable profiles of potent growth inhibition of cancer cells. , Goniocin is the only acetogenin that has an all- trans tris-THF ring unit in the C 10 –C 21 chain. Although the intriguing structure and potent cytotoxic activity of 1 against cancer cell lines at very low concentrations are attractive, this compound has not been fully investigated.…”

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confidence: 99%

Construction of Iterative Tetrahydrofuran Ring Units and Total Synthesis of (+)-Goniocin

et al. 2016

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Cytotoxic acetogenin (+)-goniocin has been synthesized in 17 steps from (R)-O-tritylglycidol. The core structure of the contiguous C22-C10 threo-trans-threo-trans-threo-trans-tris-tetrahydrofuran (THF) ring involving an iterative THF-ring unit was synthesized. An iterative THF ring unit was constructed from an alkenyl-substituted THF ring in four steps including a Pd(II)-catalyzed ring-closing reaction and cross-metathesis. This method is general and allows the preparation of both trans-threo-trans- and trans-threo-cis-THF ring units flexibly.

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A Decade of Muricatacin Synthesis and Beyond

et al. 2020

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In this review, we have abstracted the various syntheses of both enantiomers of muricatacin (a member of a bigger class of acetogenins, ACGs), over the last decade (2010–2020). Developments in the synthesis of various epimers, homologues, oxa‐analogues, δ‐lactones, and the furofuranone analogues are also enfolded in this review. Most of the synthesis involve chiral pool and catalytic enantioselective approaches, while a few are hinged on the use of chiral auxiliary and resolution methods. Muricatacin with orthogonally differentiated two oxy‐functions also serve as a start point in the synthesis of higher molecules of the acetogenin family, for example, cis‐solamins, and these have also been covered herein.

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Current Topics of the Inhibitors of Mitochondrial Complex I

Cited by 3 publications

References 76 publications

Radioligand Recognition of Insecticide Targets

Radioligand Recognition of Insecticide Targets

Construction of Iterative Tetrahydrofuran Ring Units and Total Synthesis of (+)-Goniocin

A Decade of Muricatacin Synthesis and Beyond

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