Guoen Shi

Recent advances in annonaceous acetogenins

Annonaceous acetogenins are waxy substances consisting of C32 or C34 long chain fatty acids which have been combined with a propan-2-ol unit at C-2 to form a gama-lactone. They are only found in several genera of the plant family, Annonaceae. Their diverse bioactivities as antitumour, immunosuppressive, pesticidal, antiprotozoal, antifeedant, anthelmintic and antimicrobial agents have attracted more and more interest worldwide. Recently, we reported that the Annonaceous acetogenins can selectively inhibit the growth of cancerous cells and also inhibit the growth of adriamycin resistant tumour cells. As more acetogenins have been isolated and additional cytotoxicity assays have been conducted, we have noticed that, al(hough most acetogenins have high potencies among several solid human tumour cells lines, some of the derivatives within the different structural types and some positional isomers show remarkable selectivities among certain cell lines, e.g. against prostate cancer (PC-3).

Comparative SAR evaluations of annonaceous acetogenins for pesticidal activity

The activities of 44 Annonaceous acetogenins, which were originally isolated by monitoring plant fractionations with the brine shrimp lethality test (BST), were evaluated in the yellow fever mosquito larvae microtiter plate (YFM) assay. The results clearly demonstrate that most acetogenins have pesticidal properties. The structure–activity relationships indicate that the compounds bearing adjacent bis-THF (tetrahydrofuran) rings with three hydroxyl groups are the most potent. Bullatacin (1) and trilobin (7) gave the best activities against YFM with LC50 values of 0·10 and 0·67 mg litre-1, respectively. Compounds showing LC50 values below 1·0 mg litre-1 in this assay are usually considered significant as new lead candidates for pesticidal development. In the BST, the corresponding LC50 values were 1·6×10-3 (1) and 9·7×10-3 (7) mg litre-1. This is the first report of pesticidal structure–activity relationships for a series of Annonaceous acetogenins which are known to act, at least in part, as potent inhibitors of mitochondrial NADH: ubiquinone oxidoreductase.

Bioactive annonaceous acetogenins from Rollinia mucosa

Two new bioactive Annonaceous acetogenins, rollitacin (1) and rollinacin (2), along with one known acetogenin, javoricin, were isolated from the ethanolic extract of the leaves of Rollinia mucosa. Compounds 1 and 2 exhibited selective inhibitory effects among six human solid tumour cell lines. The structural elucidations of 1 and 2 were achieved by various spectroscopic analyses and chemical derivatizations.

Applying Mosher's method to acetogenins bearing vicinal diols. The absolute configurations of muricatetrocin C and rollidecins A and B, new bioactive acetogenins from Rollinia mucosa

Muricatetrocin C (1), rollidecin A (2), and rollidecin B (3), three new bioactive annonaceous acetogenins bearing vicinal diols, were isolated from the leaves of Rollinia mucosa (Annonaceae) using activity-directed fractionation. The total structural elucidations of 1-3, including the absolute stereochemistries of the vicinal diols, were achieved by analyzing their per-Mosher ester derivatives. All three compounds showed potent and selective inhibitory effects against several human cancer cell lines.

Aromin and aromicin, two new bioactive annonaceous acetogenins, possessing an unusual bis-THF ring structure, from Xylopia aromatica (Annonaceae)

Abstract Our continuing activity-directed search for new bioactive compounds led to the isolation of two new, unusual, acetogenins, aromin (1) and aromicin (2), from the stem bark of Xylopia aromatica (Annonaceae). Both represent a new type of non-adjacent, bis-THF ring acetogenins (one THF ring being at C-4 to C-7 and the other at C-16 to C-19). Both show significant cytotoxicities among six human tumor cell lines; however, the activity is notably reduced compared to other non-adjacent bis-THF ring acetogenins. The structures of 1 and 2 were elucidated by spectroscopic methods and by derivatization.

Isolation of new bioactive annonaceous acetogenins from Rollinia mucosa guided by liquid chromatography/mass spectrometry

Reversed-phase high-performance liquid chromatography (RP-HPLC) fractionation, monitored by liquid chromatography/electrospray mass spectrometry (LC/ESI-MS), led to the isolation of two new bioactive annonaceous acetogenins, rollidecin C (1) and rollidecin D (2), from the bioactive aqueous methanol fraction of the leaves of Rollinia mucosa (Annonaceae). The structures were confirmed by analyses of the 1H and 13C NMR data. In addition, a known adjacent bis-tetrahydrofuran (THF) acetogenin, desacetyluvaricin (3), was isolated from this plant for the first time utilizing the LC/ESI-MS monitoring approach. Compound 1 exhibited selective cytotoxicity toward the colon tumor cell line (HT-29), while 2 showed only borderline cytotoxicity in a panel of six human tumor cell lines.

Additional bioactive annonaceous acetogenins from Asimina triloba (Annonaceae)

Trilobalicin (1), a new nonadjacent bis-THF ring annonaceous acetogenin, 2,4-cis- (2) and 2,4-trans-trilobacinone (3), the ketolactones of trilobacin, an adjacent bis-THF ring acetogenin, were isolated from the stem bark of Asimina triloba (L.) Dunal (Annonaceae). Their structures were established based on chemical and spectral evidence. The relative stereochemistry of 1 was determined as trans/threo/threo/trans/erythro from C-10 to C-22 by comparisons of NMR data with those of model compounds. Compound 1 is the first example of a nonadjacent bis-THF acetogenin being isolated from the title species and represents a new type of these compounds. Bioactivities of these new structures against brine shrimp larvae and six human solid tumor cell lines were determined, and cytotoxic selectivities were shown for the lung (A-549) and breast (MCF-7) cell lines with up to a million times the potency of adriamycin.

4-Acetyl Annonacin and 4-Acetyl Xylomaticin: Two Novel Bioactive Mono-Tetrahydrofuran Annonaceous Acetogenins from Asimina Longifolia (Annonaceae)

Abstract Two novel bioactive acetogenins, 4-acetyl annonacin (1) and 4-acetyl xylomaticin (2), were isolated from the leaves and twigs of Asimina longifolia K. (Annonaceae) by directing the fractionation with the brine shrimp lethality test. 1 and 2 each has a mono-tetrahydrofuran (THF) ring with two flanking hydroxyl groups and an α, β-unsaturated γ-lactone with a 4-acetoxyl. The presence of acetoxyl groups is a feature rarely found in the Annonaceous acetogenins. 1 and 2 showed potent and selective cytotoxicities among six human tumor cell lines.

A Novel Application of Mosher's Method to Epimeric Carbinols in Acetogenins; Absolute Configurations of 12-Hydroxy-Bullatacins A and B, New Acetogenins from Rollinia Mucosa

Abstract A novel application of Moshers method to epimeric carbinols is described and demonstrated in eight known Annonaceous acetogenins. The procedure requires the preparation and analysis of either the R or S Mosher esters. As an example, the absolute stereochemistries of 12-hydroxy-bullatacins A and B, two new epimeric acetogenins from Rollinia mucosa, were determined by this new procedure.