Natural acetogenins from annonaceae, synthesis and mechanisms of action

Zafra‐Polo, M. Carmen; Figadère, Bruno; Gallardo, Teresa; Tormo, José R.; Cortés, Diego

doi:10.1016/s0031-9422(97)00917-5

Cited by 189 publications

(101 citation statements)

References 111 publications

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“…NADH oxidase assay reflects the activity of the entire respiratory chain measuring the oxidation of ACG in the enzyme inhibition assays (Table 2). Annonacinone (2), which can be obtained from Annona glabra NADH by endogenous ubiquinone in complex I. The NADH:ubiquinone oxidoreductase assay reflects the and from derivatization of the parent compound 1, presented the highest increase in potency in the enzyme specific activity that requires addition of decylubiquinone (DB) as the ubiquinone-like substrate to submito-inhibition assays, followed by the natural ACG 4 and 5 that were the second most potent compounds in the chondrial particles (SMP) from beef heart; as described by Estornell et al, rotenone is the control for these en-NADH oxidase and NADH:DB oxidoreductase inhibition assays, respectively.…”

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confidence: 99%

“…The inhibition of this target by the ACG mediates their cytotoxic, antitumor, antiparasitic, threo/cis/erythro relative configuration (22). That subgroup had been described as one of the most potent sub-and insecticidal properties (2)(3)(4)(5)(6). Recently, complex I has been selected as a new target in the evaluation of groups among the ACG, represented by the prototypical rolliniastatin-1, originally isolated from Rollinia mem-insecticides and drugs against multidrug-resistant tumors (4,(7)(8)(9).…”

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confidence: 99%

“…Recently, complex I has been selected as a new target in the evaluation of groups among the ACG, represented by the prototypical rolliniastatin-1, originally isolated from Rollinia mem-insecticides and drugs against multidrug-resistant tumors (4,(7)(8)(9). Among the large number of structurally differbranacea seeds (2,16).…”

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confidence: 99%

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In Vitro Antitumor Structure–Activity Relationships of threo/trans/threo mono-Tetrahydrofuranic Acetogenins: Correlations With Their Inhibition of Mitochondrial Complex I

et al. 2003

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In this study we evaluated a mono-tetrahydrofuranic subgroup of natural acetogenins that had shown in previous enzyme inhibition studies different potency trends compared with the bis-tetrahydrofuranic acetogenin subgroup. The compounds were tested against colon, breast, lung, liver, and ovarian tumor cell lines. A drug-resistant ovarian cell line was also included in the panel. In general the compounds were more potent than doxorubicin. The goal was to determine how well the mitochondrial complex I inhibition correlates with the in vitro antitumor potency of these natural mono-tetrahydrofuranic acetogenins and of some derivatives. The results indicate that both the reduction of the terminal gamma-lactone after its translactonization and the introduction of an hydroxylimine group in the alkyl chain, near the mono-tetrahydrofuranic moiety, increased the antitumor activity, even against the doxorubicin-resistant cell line.

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Section: Resultsmentioning

confidence: 99%

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In Vitro Antitumor Structure–Activity Relationships of threo/trans/threo mono-Tetrahydrofuranic Acetogenins: Correlations With Their Inhibition of Mitochondrial Complex I

et al. 2003

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“…(3) The crude extracts of Uvaria chamae are widely used in traditional medicinal practices for the treatment of a range of ailments including parasitic-borne West African sleeping sickness and has proven to be a rich source of novel acetogenins. (4) An initial biological screening of chamuvarinin showed significant cytotoxicity toward KB 3-1 cervix cancer cell lines (IC 50 = 0.8 nM).…”

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Synthesis and Stereochemical Assignment of (+)-Chamuvarinin

Florence

Morris²,

Murray³

et al. 2010

Org. Lett.

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A stereocontrolled total synthesis of (+)-chamuvarinin, isolated from the root extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the adjacently linked C15−C28 ether array, followed by a late-stage Julia−Kocienski olefination to append the butenolide motif. This constitutes the first total synthesis of (+)-chamuvarinin, defining the relative and absolute configuration of this unique annonaceous acetogenin.

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“…Using systematically selected natural and synthetic THF-type acetogenins, Miyoshi and colleagues revealed that the alkyl spacer linking the γ-lactone and the hydroxylated THF moieties dynamically regulate the binding of these two toxophores to the putative binding sites. 1 So far, over 430 acetogenins have been isolated from Annonaceae, [2][3][4] however, only 8 compounds contain a THP ring. Consequently, significant efforts have been devoted toward synthesis of THP-containing acetogenins due to their unique structures.…”

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confidence: 99%