Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I

Tormo, José R.; Gallardo, Teresa; Aragón, Raúl; Cortés, Diego; Estornell, Ernesto

doi:10.1016/s0009-2797(99)00120-9

Cited by 65 publications

(69 citation statements)

References 33 publications

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“…For example, rotenone only partially inhibits Complex I (even at very large doses, the maximum inhibition is around 90%). Moreover, most inhibitors are actually competitive with one another and the only way to categorize them has been through different kinetics (139,144). Even with these studies, it is not clear whether there exists a single binding site for all inhibitors or whether different inhibitors bind at different sites with different affinities.…”

Section: Production At Complex Imentioning

confidence: 99%

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Muller

2000

AGE

120

123

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Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/ transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.

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Section: Production At Complex Imentioning

confidence: 99%

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Muller

2000

AGE

120

123

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“…Annonaceous acetogenins are strong inhibitors of ATP production (Adenosine triphosphate) in the mitochondrial complex I (NADH ubiquinone oxidoreductase) in insects, and this reduction in ATP production may lead cells to apoptosis (programmed cell death) (Lewis et al 1993;Ahammadsahib et al 1993;Tormo et al 1999). In addition, acetogenins have characteristics of compounds that interfere in the hormonal activity of lepidopterans.…”

Section: Discussionmentioning

confidence: 99%

Annona crassiflora Mart. (Annonaceae): effect of crude extract of seeds on larvae of soybean looper Chrysodeixis includens (Lepidoptera: Noctuidae)

2017

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ABSTRACT:The effect of a crude extract of Annona crassiflora was evaluated on larvae of the soybean looper, Chrysodeixis includens (Lepidoptera: Noctuidae) in different stages of larval development.The extract was prepared with seeds of A. crassiflora fruits collected in the state of Mato Grosso, Brazil. The extract was diluted in water and solubilizer agent at the concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0%; it was tested by ingestion of treated leaves and contact. The mortality rate of topically treated caterpillars of first, third, and fifth instars was significantly higher than that of the control group. For first instar caterpillars, mortality was observed within the first 24 h after application, while, for the remaining instars, it was significant after 72 h. For caterpillars fed treated leaves, no differences in mortality rates were observed within the first 120 h. These caterpillars were monitored until the end of the larval stage, during which mortality rates increased for first and third instar caterpillars. The mortality rate of fifth instar larvae was not significantly different between treatments. The treatment by ingestion was not efficient over a short period of time, but reduced the number of caterpillars that completed their development, decreasing the number of insects in the following generation. We concluded that the crude extract of A. crassiflora affected the development of C. PLANT PROTECTION -includens and is a promising compound for the control of this pest.

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“…As ACG only inhibit complex I, the decrease of NADH oxidase activity is directly attributed to the inhibition of complex I. 5) Most studies suggest that the terminal g-lactone is essential for the potency of ACG as complex I inhibitors, although some reports propose that the alkyl chain plays a more crucial role. However, for the roles of other ring moieties have not been sufficiently emphasized.…”

Section: )mentioning

confidence: 99%

Inhibitory Activities of Three Annonaceous Acetogenins on NADH Oxidase of Chicken Liver Mitochondria

Wei

Xie

et al. 2003

Biological & Pharmaceutical Bulletin

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Annonaceous acetogenins (ACG) are natural products isolated from plants of the family Annonaceae and which have potent biological activities. Since Jolad isolated the first acetogenin (uvaricin) from Uvaria acuminata in 1982, 1) almost 400 acetogenins have been discovered, and new structural ACG will be isolated from other plants along as they are studied in depth. The reasons that ACG have drawn so much attention are not only their novel structural features but also their potent and broad activities which are seldom found in other natural compounds.The general structures of ACG are characterized by long alkyl chain compounds of 35-37 carbons containing terminal 2,4-disubstituted-g-lactone, zero to three tetrahydrofuran (THF) rings, and a number of oxygenated moieties (hydroxyls, acetoxyls, ketones, epoxides) or double bonds. According to the number and stereochemistry of THF, ACG have been classified into mono-THF, adjacent bis-THF, non-adjacent bis-THF, tri-THF, non-THF, and non-classical acetogenins. 2)Because of the wide use of ACG in pesticidal, antimalarial, antimicrobial, antiparasitic, antiprotozoal, cytotoxic activities and antitumor effects, studies on the isolation and identification of ACG as well as their action mechanism are a field presently focused on.ACG show potent activities by inhibiting NADHubiquinone oxidoreductase (complex I) in mitochondrial respiratory chain, and complex I is the largest, most complicated and important protein complex of the mitochondrial electron transport systems, which are related to ATP production.2,3) Additionally, ACG are also strong inhibitors of NADH oxidase of the plasma membrane in cancer cells, but not in rat liver plasma membrane. 4) Actually, complex I can be evaluated by NADH-ubiquinone oxidoreductase activity or by NADH oxidase activity in mitochondria, although they are not equivalent. NADH oxidase activity represents an integrated activity in which NADH is oxidized and the electrons are transferred along the respiratory chain to be finally accepted by molecular oxygen. Otherwise, the assay of NADHubiquinone oxidoreductase activity is performed with ubiquinone or its analogue as electron acceptor. As ACG only inhibit complex I, the decrease of NADH oxidase activity is directly attributed to the inhibition of complex I. 5)Most studies suggest that the terminal g-lactone is essential for the potency of ACG as complex I inhibitors, although some reports propose that the alkyl chain plays a more crucial role. However, for the roles of other ring moieties have not been sufficiently emphasized. In the present study, the roles of these structural factors are discussed by three acetogenins inhibiting NADH oxidase of chicken liver mitochondria with different ring moieties in addition to terminal g-lactone, especially the non-THF type compound exhibiting inhibitory activity, and in comparison with rotenone which is the classic inhibitor of complex I. MATERIALS AND METHODS Materials and ReagentsThree acetogenins were isolated and purified from seeds of Annona squamo...

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Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I

Cited by 65 publications

References 33 publications

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging

Annona crassiflora Mart. (Annonaceae): effect of crude extract of seeds on larvae of soybean looper Chrysodeixis includens (Lepidoptera: Noctuidae)

Inhibitory Activities of Three Annonaceous Acetogenins on NADH Oxidase of Chicken Liver Mitochondria

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