Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay

Oberlies, Nicholas H.; Jones, Julie L.; Corbett, Thomas H.; Fotopoulos, Sophia S.; McLaughlin, Jerry L.

doi:10.1016/0304-3835(95)92759-7

Cited by 93 publications

(71 citation statements)

References 17 publications

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“…Cancer cells had an unusual action mechanism of energy conservation such as higher respiration and energy production, and this kind of energy metabolism made it more easily inhibited by ACG than normal cells. 15) However, ACG were fairly toxic to normal cells in vivo or vitro, their toxicity was hundreds or thousands of times higher than KCN, which is a virulent chemical reagent. 16) This resulted in the restricted use of ACG as anticancer drugs in the clinical area.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…符合本综述要求的化合物为 55 个(见表 1). 除了本文总结的构效关系之外, 据文献报道 [7,10,12,38] , 单四氢呋喃型番荔枝内酯尤其是无 4-OH 时活性最低, 而邻双四氢呋喃型番荔枝内酯活性最高, 其次是间双四氢呋喃型番荔枝内酯. α,α'-二羟基取代邻双四氢呋喃型番荔枝内酯类化合物的活性要强于 α-单羟基取代邻双四氢呋喃型番荔枝内酯类化合物 [22] .…”

Section: 邻位双四氢呋喃型 Thf 两侧各有一个羟基相邻的相对构型有 Th/t/th/t/th Eunclassified

Progress in Structure Activity Relationship of Natural Annonaceous Acetogenins

Chen¹,

Li²,

Chen³

2012

Chin. J. Org. Chem.

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“…Both mechanisms of action result in the inhibition of ATP production and may account for the observation that AGEs are more effective at killing multiple-drug resistant (MDR) tumours than their nonresistant counterparts since the MDR pumps on the cell membranes require ATP to function. In addition, Oberlies et al observed that AGEs could selectively inhibit the cell growth of cancerous cells by in vitro cell inhibition assays against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancer cell lines [69]. Interestingly, the work of Oberlies et al proposed that this class of natural products showed a certain biological activity against some drug-resistant cancers.…”

Section: Biological Activities and The Mechanisms Of Action Of The Agesmentioning

confidence: 99%

Historic Perspectives on Annonaceous Acetogenins from the Chemical Bench to Preclinical Trials

Liaw¹,

Wu²,

Chang³

et al. 2010

Planta Med

113

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Studies on the Annonaceous acetogenins began after the first cytotoxic acetogenin, uvaricin, was isolated in 1982. This attractive finding made many medicinal and natural product chemists direct their efforts on the isolation and identification of these classes of compounds. As more Annonaceous acetogenins were isolated, more information about them was uncovered. From their structural identification to the total synthesis of natural product analogues and from cell-based screening and molecular-based targeting to animal testing, the mechanisms of action of the Annonaceous acetogenins became clearer. The purpose of this review is to give an account of recent studies on this class of compounds and their analogues, which will aid us not only in clarifying how the Annonaceous acetogenins act but also in establishing principles for the further development of this class of compounds

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Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay

Cited by 93 publications

References 17 publications

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

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

Progress in Structure Activity Relationship of Natural Annonaceous Acetogenins

Historic Perspectives on Annonaceous Acetogenins from the Chemical Bench to Preclinical Trials

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