Cytotoxic Acetogenins from the Roots of Annona purpurea

Abstract

Annona purpurea, known in Mexico as “cabeza de negro” or “ilama”, belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A–E (1–5). These compounds have an aliphatic chain of 37 carbons with a terminal α,β unsaturated γ-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) α-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF α,α’-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1–4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM).

HPLC‐DAD method for the detection of five annopurpuricins in root samples ofAnnona purpurea

“…In the hexane extracts, only annopurpuricins B and E were quantified (Table ). There, the identity of annopurpuricin B was also confirmed by its isolation and structural characterization . However, annopurpuricin E has an epoxide system showing lipophilicity higher compared to other compounds, which would explain its presence in a sample of low polarity (Table ).…”

“…In both batches of DCM, the isolation and unambiguous identification of the acetogenins present was carried out following the procedure described by Hernández‐Fuentes et al . Furthermore, it was possible to quantify, annopurpuricins B and D in the DCM extract of the sample obtained from Coalcoman, Michoacan. Both compounds are isomers and, the separation was possible because of annopurpuricin D can be precipitated causing its separation from the liquid phase and thus allowing its quantification; thus, concentration of annopurpuricin B was calculated by subtracting annopurpuricin D concentration to the total annopurpuricin B/D.…”

“…The five reference compounds annopurpuricins A and B [adjacent bis‐tetrahydrofuran (THF) α‐monohydroxylated type], annopurpuricin C (adjacent bis‐THF α, α′‐dihydroxylated type), annopurpuricin D (adjacent bis‐THF α,α′‐dihydroxylated type with OH at C‐4), and annopurpuricin E (bis‐epoxide system with cis ‐double bond), were previously isolated from A. purpurea roots and their structures (Figure ) were established by spectroscopic and spectrometric analysis …”

“…Recently, five new bioactive acetogenins, annopurpuricins A–E, were isolated from the Annona purpurea root. These molecules showed high cytotoxicity in cancer cell lines at subnanomolar range …”

Effects of Acetogenins from Annona coriacea on the in Vitro Reactions of Photosynthesis

“…These polyketides have 35 or 37 carbon atoms and also are constituted by an aliphatic chain with an α,β-unsaturated γ-lactone ring and up to three tetrahydrofuran (THF) rings. [6,7] Several reports can be found in the literature concerning biological properties related to these compounds: cytotoxic, [6,8] antiangiogenic, [9] neurotoxic, [10] larvicidal, [11] and also their agrochemical effects. [7] Especially in the agronomic field, we highlight the nematicidal, [12] insecticidal [13][14][15] and herbicidal properties, but for this last one, the reports remain incipient.…”