Abstract
Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from Annona cherimola leaves, an agricultural waste, has not been reported to date. Molvizarin (1) cherimolin-1 (2), motrilin (3), annonacin (4) and annonisin (5) are isolated for the first time from A. cherimola deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 µM (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 µM, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 µM, 24 h, 92% live cells). These results highlight the use of by-products of A. cherimola, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy.
Highlights
Annonaceous acetogenins (ACGs) are fatty-acid derived natural products found only in species of the Annonaceae family [1]
The isolation of ACGs from Annona cherimola leaves has not been reported to date
The present study shows the isolation of five ACGs that are described for the first time in A. cherimola deciduous leaves
Summary
Annonaceous acetogenins (ACGs) are fatty-acid derived natural products found only in species of the Annonaceae family [1]. More than 400 ACGs—obtained mainly from roots, stems, seeds and, less often, from leaves [2]—have been described in the last few decades. These compounds contain a long aliphatic fatty acid chain with 35–37 carbon atoms, derived from the polyketide pathway [3], a terminal methyl-substituted α,β-unsaturated γ-lactone ring and either none, one, two or three tetrahydrofuran (THF) rings that can be adjacent or not adjacent to Molecules 2020, 25, 4861; doi:10.3390/molecules25204861 www.mdpi.com/journal/molecules. The biological activity is influenced by the number and stereochemistry of the THF rings and the number of carbon atoms between the polar core and the γ-unsaturated lactone [5]. It is considered optimum for activity to have at least 13 carbons in the spacer [6]
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