Two new sesquiterpene coumarins, designated 5'-acetoxy-8'-hydroxyumbelliprenin (1) and 10'R-acetoxy-11'-hydroxyumbelliprenin (2), and a new diterpene, 15-hydroxy-6-en-dehydroabietic acid (3), along with 27 known compounds, were isolated from a CHCl(3)-soluble extract of Ferula assa-foetida through bioassay-guided fractionation. The structures of the new metabolites 1-3 were identified by spectroscopic data interpretation and by the Mosher ester method. Compounds 4 and 6-13 showed greater potency against influenza A virus (H(1)N(1)) (IC(50) 0.26-0.86 microg/mL) than amantadine (IC(50) 0.92 microg/mL), and 11 exhibited the best potency (IC(50) 0.51, 2.6, and 3.4 microg/mL) of these compounds against the HepG2, Hep3B, and MCF-7 cancer cell lines, respectively.

Studies on the Annonaceous acetogenins began after the first cytotoxic acetogenin, uvaricin, was isolated in 1982. This attractive finding made many medicinal and natural product chemists direct their efforts on the isolation and identification of these classes of compounds. As more Annonaceous acetogenins were isolated, more information about them was uncovered. From their structural identification to the total synthesis of natural product analogues and from cell-based screening and molecular-based targeting to animal testing, the mechanisms of action of the Annonaceous acetogenins became clearer. The purpose of this review is to give an account of recent studies on this class of compounds and their analogues, which will aid us not only in clarifying how the Annonaceous acetogenins act but also in establishing principles for the further development of this class of compounds

Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I (2), and cis-annomontacin (3), along with five known acetogenins, annonacin, annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous acetogenins, cis-corossolone (4) and annocatalin (5), together with four known ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the leaves of this species. The structures of all new isolates were elucidated and characterized by spectral and chemical methods. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G(2) and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line.

Several bioactive acetogenins were selective against 1A9 (ovarian cancer) cell replication but did not show a corresponding hyperactivity against other cell lines. The most active compound (26, molvizarin) was a selective inhibitor of 1A9 cell replication with a potency (ED(50) = 5 pg/mL) of over 1 million times more than that for other cell lines.

Two new protopine-type alkaloids, argemexicaine A (1) and argemexicaine B (2), along with thirteen known alkaloids, were isolated from MeOH extracts of Formosan Argemone mexicana L. (Papaveraceae). Physical and spectral analyses, particularly IR and thermo-modulated 1D and 2D NMR, were used to determine the transannular conformations of the isolated protopine-type alkaloids. The known benzo[ c]phenanthridine (+/-)-6-acetonyldihydrochelerythrine (5) exhibited significant anti-HIV activity in H9 lymphocytes with EC50 and TI (Therapeutic Index) values of 1.77 microg/mL and 14.6, respectively.

Bioactivity-guided fractionation led to the isolation of two new Annonaceous acetogenins, annocatacin A ( 1). and annocatacin B ( 2). from the seeds and the leaves, respectively, of Annona muricata. Compounds 1 and 2 are the first examples where the adjacent bis-tetrahydrofuran ring system is located at C-15. The new structures were elucidated and characterized by spectral and chemical methods. Both Annonaceous acetogenins 1 and 2 showed significant in vitro cytotoxicity toward the human hepatoma cell lines, Hep G2 and 2,2,15, and were compared with the known adjacent bis-tetrahydrofuran acetogenins, neoannonin ( 3). desacetyluvaricin ( 4). bullatacin ( 5). asimicin ( 6). annoglaucin ( 7). squamocin ( 8). and rollimusin ( 9).

In recent decades, annonaceous acetogenins have become highly studied plant secondary metabolites in terms of their isolation, structure elucidation, synthesis, biological evaluation, mechanism of action, and toxicity. The aim of the present contribution is to summarize chemical and biological reports published since 1997 on annonaceous acetogenins and synthetic acetogenin mimics. The compounds are considered biologically in terms of their cytotoxicity for cancer cell lines, neurotoxicity, pesticidal effects, and miscellaneous activities.

During our search for anti-tumor agents from pteridophytes, three new flavonoids, protoapigenone (1), 5',6'-dihydro-6'-methoxyprotoapigenone (2), and protoapigenin (3), along with four known compounds, protoapigenin 4'- O-beta- D-glucoside (4), apigenin 4'- O-beta- D-glucoside (5), kaempferol 3- O-alpha- L-rhamnopyranoside (6), kaempferol 3,7-di- O-alpha- L-rhamnopyranoside (7), were isolated from Thelypteris torresiana using bioactivity-guided fractionation methods . The structures of the new isolates were elucidated by 1D- and 2D-NMR spectral analysis. Among the 7 compounds, protoapigenone (1) exhibited significant anti-tumor activities toward Hep G2, Hep 3B, MCF-7, A549, and MDA-MB-231 with IC50 values of 1.60, 0.23, 0.78, 3.88 and 0.27 microg/mL, respectively.