Annonaceous Acetogenins:  Recent Progress

Alali, Feras Q.; Liu, Xiaoxi; McLaughlin, Jerry L.

doi:10.1021/np980406d

Cited by 785 publications

(553 citation statements)

References 113 publications

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“…The ethanol extracts were evaporated to dryness under vacuum using a rotary evaporator (Rotavapor Buchi, Swizterland) and weighed. Each extract was further fractionated by liquid-liquid partition as previously described (Alali et al, 1999). Briefly, ethanolic residues were partitioned between dichloromethane and water (1:1) to yield water and dichloromethane fractions as well as interface precipitates.…”

Section: Plants Extraction and Fractionationmentioning

confidence: 99%

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia (Annonaceae)

Mfopa¹,

Mbouna²,

Tchokouaha³

et al. 2017

Int. J. Bio. Chem. Sci

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The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography. The antiplasmodial effect of extracts, fractions and subfractions against P. falciparum Chloroquine resistant (PfK1) strain was determined using SYBR green florescence assay. The promising fraction was assessed for cytotoxicity against Human Foreskin Fibroblast (HFF) cells and further for safety in Swiss albino mice and suppressive effect against P. berghei. The methanol sub-fraction of P. suaveolens [PStw(Ace)] showed the highest potency with IC 50 of 3.24 µg/mL. Sub-fraction PS8 from PStw(Ace) was the most active with IC 50 of 4.42 µg/mL. Oral administration of PStw(Ace) at 5000 mg/kg b.w in mice showed no signs of toxicity. Also, it exerted the highest suppressive effect against P. berghei at 400 mg/kg b.w throughout the 4 days experiment. Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the PStw(Ace) fraction might be of interest in future development of an antimalarial phytodrug.

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Section: Plants Extraction and Fractionationmentioning

confidence: 99%

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia (Annonaceae)

Mfopa¹,

Mbouna²,

Tchokouaha³

et al. 2017

Int. J. Bio. Chem. Sci

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“…These compounds have shown important biological activities, including antiparasitic, in particular against Leishmania sp., Plasmodium falciparum, and Trypanosoma cruzi. [4][5][6][7][8][9][10][11][12] Annona amazonica R.E. Fries is a tropical tree that grows up to 20-25 m tall and 35-60 cm in diameter, and is found from Panama to South America.…”

Section: Introductionmentioning

confidence: 99%

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Pinheiro

Xavier

Souza

et al. 2009

J. Braz. Chem. Soc.

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O presente trabalho descreve o isolamento, a partir do caule de Annona amazonica, do ácido acantóico, um diterpeno do tipo pimaradieno que possui várias e importantes atividades biológicas descritas na literatura. Neste estudo foi verificado que este composto apresenta significante atividade tripanocida contra as formas epimastigotas de Trypanosoma cruzi. Também foi constatado que este diterpeno é o constituinte majoritário da planta, encontrado em cerca de 65% do extrato hexânico, demonstrando que A. amazonica é uma nova fonte natural renovável desta substância. Além do ácido acantóico, a investigação química resultou no isolamento dos alcalóides liriodenina e cassiticina, entre outros compostos, tais como terpenos, esteróides e ácidos graxos. Adicionalmente, é descrita a completa e inequívoca atribuição dos deslocamentos químicos de RMN de 1 H e 13 C da cassiticina.The present work reports the isolation of acanthoic acid, a promising pimaradiene-type diterpene with several important biological activities described in the literature, from the stems of Annona amazonica. We found that acanthoic acid has significant trypanocidal activity against the epimastigote forms of Trypanosoma cruzi. This diterpene is the major constituent of the plant, comprising at least 65% of the hexane extract, demonstrating that A. amazonica is a new renewable natural source for this compound. The chemical investigation also resulted in the isolation of the alkaloids liriodenine and cassythicine, and other compounds including terpenes, sterols, and fatty acids. Additionally, the complete and unequivocal 1 H and 13 C NMR chemical shift assignments for cassythicine are provided. Keywords: Annona amazonica, Annonaceae, acanthoic acid, cassythicine, trypanocidal activity IntroductionThe family Annonaceae, comprised of tropical and subtropical species with about 135 genera and more than 2500 species and widely distributed in South and Central America, Africa, Asia, and Australia, 1 is known for its edible fruits and the medicinal properties of several species. 2 In Brazil, there are 26 genera with about 260 species, including the genus Annona, which contains approximately 120 species. 3 Chemical investigations of species of Annonaceae have revealed their high chemical diversity in terms of secondary metabolites, such as alkaloids, acetogenins, terpenoids and lactones. These compounds have shown important biological activities, including antiparasitic, in particular against Leishmania sp., Plasmodium falciparum, and Trypanosoma cruzi. [4][5][6][7][8][9][10][11][12] Annona amazonica R.E. Fries is a tropical tree that grows up to 20-25 m tall and 35-60 cm in diameter, and is found from Panama to South America. In Brazil this species commonly occurs in the Amazon, mainly in the states of Amazonas and Pará. 13 To the best of our knowledge, only one previous phytochemical study has described the isolation and identification of cyanogenic constituents from this species. 14 Here we describe the isolation and structural identification of the chemica...

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“…The inhibitory effect of acetogenins on mitochondrial NADH-ubiquinone oxidoreductase (complex I) 1 is of particular importance since their diverse biological activities are thought to be attributable to this effect (3). Some acetogenins, such as bullatacin ( Figure 1) and rolliniastatin 1, are the most potent inhibitors of bovine heart mitochondrial complex I identified to date (4)(5)(6)(7).…”

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confidence: 99%

“…The structural features of ∆lac-acetogenins are highly unique compared to those of ordinary complex I inhibitors and rather resemble amphiphilic phospholipid or detergent molecules. Interestingly, the ∆lac-acetogenin carrying two n-undecanyl groups (compound 1 in Figure 1) elicited very potent inhibition with bovine heart mitochondrial complex I despite the lack of an R, -unsaturated γ-lactone ring, which is one of the common structural features of a large number of natural acetogenins (1)(2)(3). Double-inhibitor titration of steady-state complex I activity showed that the inhibition of compound 1 and bullatacin is not additive, suggesting that the binding sites of the two inhibitors are not identical (8).…”

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confidence: 99%

Synthesis and Inhibition Mechanism of Δlac-Acetogenins, a Novel Type of Inhibitor of Bovine Heart Mitochondrial Complex I

et al. 2004

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We have synthesized ∆lac-acetogenins that are new acetogenin mimics possessing two n-alkyl tails without an R, -unsaturated γ-lactone ring and suggested that their inhibition mechanism may be different from that of common acetogenins [Hamada et al. (2004) Biochemistry 43, 3651-3658]. To elucidate the inhibition mechanism of ∆lac-acetogenins in more detail, we carried out wide structural modifications of original ∆lac-acetogenins and characterized the inhibitory action with bovine heart mitochondrial complex I. In contrast to common acetogenins, both the presence of adjacent bis-THF rings and the stereochemistry around the hydroxylated bis-THF rings are important structural factors required for potent inhibition. The inhibitory potency of a derivative possessing an n-butylphenyl ether structure (compound 7) appeared to be superior to that of the original ∆lac-acetogenins and equivalent to that of bullatacin, one of the most potent natural acetogenins. Double-inhibitor titration of steady-state complex I activity showed that the extent of inhibition of compound 7 and bullatacin is not additive, suggesting that the binding sites of the two inhibitors are not identical. Competition tests using a fluorescent ligand indicated that the binding site of compound 7 does not overlap with that of other complex I inhibitors. The effects of compound 7 on superoxide production from complex I are also different from those of other complex I inhibitors. Our results clearly demonstrate that ∆lac-acetogenins are a novel type of inhibitor acting at the terminal electron-transfer step of bovine complex I.

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Annonaceous Acetogenins: Recent Progress

Cited by 785 publications

References 113 publications

<i>In vitro</i> and <i>in vivo</i> antiplasmodial activity of extracts from <i>Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia</i> (Annonaceae)

<i>In vitro</i> and <i>in vivo</i> antiplasmodial activity of extracts from <i>Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia</i> (Annonaceae)

Acanthoic acid and other constituents from the stem of Annona amazonica (Annonaceae)

Synthesis and Inhibition Mechanism of Δlac-Acetogenins, a Novel Type of Inhibitor of Bovine Heart Mitochondrial Complex I

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