Planta Med 2010; 76(13): 1390-1404
DOI: 10.1055/s-0030-1250006
Reviews
© Georg Thieme Verlag KG Stuttgart · New York

Historic Perspectives on Annonaceous Acetogenins from the Chemical Bench to Preclinical Trials

Chih-Chuang Liaw1 , 2 , Tung-Ying Wu3 , Fang-Rong Chang3 , Yang-Chang Wu3 , 4
  • 1Graduate Institute of Pharmaceutical Chemistry, College of Pharmacy, China Medical University, Taichung, Taiwan
  • 2Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan
  • 3Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 4Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Weitere Informationen

Publikationsverlauf

received Nov. 30, 2009 revised April 26, 2010

accepted April 28, 2010

Publikationsdatum:
24. Juni 2010 (online)

Abstract

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.

References

  • 1 Cragg G M, Newman D J, Snader K M. Natural products in drug discovery and development.  J Nat Prod. 1997;  60 52-60
  • 2 Wani M C, Taylor H L, Wall M E, Coggon P, McPhail A T. Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.  J Am Chem Soc. 1971;  93 2325-2327
  • 3 Wall M E, Wani M C, Cook C E, Palmer K H, McPhail A T, Sim G A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata.  J Am Chem Soc. 1966;  88 3888-3890
  • 4 Hartwell J L, Schrecker A W. Components of podophyllin. V. The constitution of podophyllotoxin.  J Am Chem Soc. 1951;  73 2909-2916
  • 5 Neuss N, Gorman M, Hargrove W, Cone N J, Biemann K, Buechi G, Manning R E. Vinca alkaloids. XXI. The structures of the oncolytic alkaloids vinblastine (VLB) and vincristine (VCR).  J Am Chem Soc. 1964;  86 1440-1442
  • 6 Arcamone F, Franceschi G, Penco S, Selva A. Adriamycin (14-hydroxydaunomycin), a novel antitumor antibiotic.  Tetrahedron Lett. 1969;  13 1007-1010
  • 7 Rupprecht J K, Hui Y H, McLaughlin J L. Annonaceous acetogenins: a review.  J Nat Prod. 1990;  53 237-278
  • 8 Zeng L, Ye Q, Oberlies H, Shi G, Gu Z M, He K, McLaughlin J L. Recent advances in annonaceous acetogenins.  Nat Prod Rep. 1996;  13 275-306
  • 9 Cave A, Figadere B, Laurens A, Cortes D. Acetogenins from Annonaceae. Progress in the chemistry of organic natural products, vol. 70. Berlin, Heidelberg; Springer Publisher 1997: 81-288
  • 10 Bermejo A, Figadere B, Zafra-Polo M C, Barrachina I, Estornell E, Cortes D. Acetogenins from Annonaceae. Recent progress in isolation, synthesis, and mechanisms of action.  Nat Prod Rep. 2005;  22 263-303
  • 11 Leboeuf M, Cave A, Bhaumik P K, Mukherjee B, Mukherjee R. The phytochemistry of the Annonaceae.  Phytochemistry. 1982;  21 2783-2813
  • 12 Wu Y C. New research and development on the Formosan annonaceous plants. Atta-ur-Rahman Studies in natural products chemistry, vol. 33. Amsterdam; Elsevier B.V. 2006: 957-1024
  • 13 Nakanishi Y, Chang F R, Liaw C C, Wu Y C, Bastow K F, Lee K H. Acetogenins as selective inhibitors of the human ovarian 1A9 tumor cell line.  J Med Chem. 2003;  46 3185-3188
  • 14 Jolad S D, Hoffmann J J, Schram K H, Cole J R. Uvaricin, a new antitumor agent from Uvaria accuminata (Annonaceae).  J Org Chem. 1982;  47 3151-3153
  • 15 McCloud T G, Smith D L, Chang C-J, Cassady J M. Annonacin, a novel, biologically active polyketide from Annona densicoma.  Experientia. 1987;  43 947-949
  • 16 Fujimoto Y, Eguchi T, Kakinuma K, Ikekawa N, Sahai M, Gupta Y K. Squamocin, a new cytotoxic bis-tetrahydrofuran containing acetogenin from Annona squamosa.  Chem Pharm Bull. 1988;  36 4802-4806
  • 17 Hui Y H, Rupprecht J K, Anderson J E, Liu Y M, Smith D L, Chang C J, McLaughlin J L. Bullatalicin, a novel bioactive acetogenin from Annona bullata (Annonaceae).  Tetrahedron. 1989;  45 6941-6948
  • 18 Cortes D, Rios J L, Villar A, Valverde S. Cherimoline et dihydrocherimoline: deux nouvelles γ-lactones bis-tetrahydrofuranniques possedant une activite antimicrobienne.  Tetrahedron Lett. 1984;  25 3199-3202
  • 19 Cortes D, Myint S H, Dupont B, Davoust D. Acetogenins of the Annonaceae. Part 20. Bioactive acetogenins from seeds of Annona cherimolia.  Phytochemistry. 1993;  32 1475-1482
  • 20 Rios J L, Cortes D, Valverde S. Acetogenins, aporphinoids, and azaanthraquinone from Annona cherimolia seeds.  Planta Med. 1989;  55 321-323
  • 21 Hoye T R, Suhadolnik J C. On the stereochemistry of the bistetrahydrofuranyl moiety of uvaricin. Proton chemical shifts can play a crucial role in complex structure determination.  J Am Chem Soc. 1987;  109 4402-4403
  • 22 Hoye T R, Zhuang Z P. Validation of the proton NMR chemical shift method for determination of stereochemistry in the bistetrahydrofuranyl moiety of uvaricin-related acetogenins from Annonaceae: rolliniastatin 1 (and asimicin).  J Org Chem. 1988;  53 5578-5580
  • 23 Pettit G R, Cragg G M, Polonsky J, Herald D L, Goswami A, Smith C R, Moretti C, Schmidt J M, Weisleder D. Isolation and structure of rolliniastat 1 from the South American tree Rollinia mucosa.  Can J Chem. 1987;  65 1433-1435
  • 24 Hui Y H, Rupprecht J K, Liu Y M, Anderson J E, Smith D L, Chang C J, McLaughlin J L. Bullatacin and bullatacinone: two highly potent bioactive acetogenins from Annona bullata.  J Nat Prod. 1989;  52 463-477
  • 25 Gawronski J, Wu Y C. A note on the determination of absolute configuration of acetogenins by circular dichroism.  Polish J Chem. 1999;  73 241-243
  • 26 Born L, Lieb F, Lorentzen J P, Moeschler H, Nonfon M, Soellner R, Wendisch D. The relative configuration of acetogenins isolated from Annona squamosa: annonin I (squamocin) and annonin VI.  Planta Med. 1990;  56 312-316
  • 27 Hoye T R, Suhadolnik J C. Symmetry-assisted synthesis of triepoxide stereoisomers of E,Z,E-dodeca-2,6,10-trien-1,12-diol and their cascade reactions to 2, 5-linked bistetrahydrofurans.  J Am Chem Soc. 1985;  107 5312-5313
  • 28 Huang T S. Flora of Taiwan, vol. 2. Taipei; Lungwei Printing Co. Ltd. 1996: 415-419
  • 29 Liao J C. A list of scientific names of woody plants in Taiwan. Taipei; College of Agriculture, National Taiwan University 1993
  • 30 Wu Y C, Chang G Y, Ko F N, Teng C M. Bioactive constituents from the stems of Annona montana.  Planta Med. 1995;  61 146-149
  • 31 Chen K S, Ko F N, Teng C M, Wu Y C. Antiplatelet and vasorelaxing actions of some aporphinoids.  Planta Med. 1996;  62 133-136
  • 32 Lin C H, Yang C M, Ko F N, Wu Y C, Teng C M. Antimuscarinic action of liriodenine, isolated form Fissistigma glaucescens, in canine tracheal smooth muscle.  Br J Pharmacol. 1994;  113 1464-1470
  • 33 Chang G J, Wu M H, Wu Y C, Su M J. Electrophysiological mechanisms for antiarrhythmic efficacy and positive inotropy of liriodenine, a natural aporphine alkaloid from Fissistigma glaucescens.  Br J Pharmacol. 1996;  118 1571-1583
  • 34 Ko F N, Yu S M, Su M J, Wu Y C, Teng C M. Pharmacological activity of (−)-discretamine, a novel vascular α-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens.  Br J Pharmacol. 1993;  110 882-888
  • 35 Wu Y C, Chang F R, Duh C Y, Wang S K, Wu T S. Cytotoxic styrylpyrrones of Goniothalamus amuyon.  Phytochemistry. 1992;  31 2851-2853
  • 36 Wu Y C, Duh C Y, Chang F R, Chang G Y, Wang S K, Chang J J, McPhail D R, McPhail A T, Lee K H. The crystal structure and cytotoxicity of goniodiol-7-monoacetate from Goniothalamus amuyon.  J Nat Prod. 1991;  54 1077-1081
  • 37 Wu Y C, Chang F R, Chen K S, Liang S C, Lee M R. Studies on acetogenins from Formosan Annonaceous plants. 3. Diepoxymontin, a novel acetogenin from Annona montana.  Heterocycles. 1994;  38 1475-1478
  • 38 Wu Y C, Chang F R, Duh C Y, Wang S K. Annoreticuin and isoannoreticuin: two new cytotoxic acetogenins from Annona reticulata.  Heterocycles. 1992;  34 667-674
  • 39 Chang F R, Wu Y C, Duh C Y, Wang S K. Studies on the acetogenins of Formosan Annonaceous plants, II. Cytotoxic acetogenins from Annona reticulata.  J Nat Prod. 1993;  56 1688-1694
  • 40 Zhang L, Yang R, Wu X. Chemical compositions of Goniothalamus howii (I).  Zhiwu Xuebao. 1993;  35 390-396
  • 41 Yu J, Luo X, Sun L, Liu C, Hong S, Ma L. Squamostatin-B, a new polyketide from Annona squamosa (Annonaceae).  Chin Chem Lett. 1993;  4 423-426
  • 42 Li C M, Mu Q, Hao X J, Sun H D, Zheng H L, Wu Y C. Three new bioactive Annonaceous acetogeninins from Annona muricata.  Chin Chem Lett. 1994;  5 747-750
  • 43 Londershausen M, Leicht W, Lieb F, Moeschler H, Weiss H. Molecular mode of action of annonins.  Pestic Sci. 1991;  33 427-438
  • 44 Gu Z M, Fang X P, Miesbauer L R, Smith D L, McLaughlin J L. 30-, 31-, and 32-hydroxybullatacinones: bioactive terminally hydroxylated Annonaceous acetogenins from Annona bullata.  J Nat Prod. 1993;  56 870-876
  • 45 Gu Z M, Fang X P, Rieser M J, Hui Y H, Miesbauer L R, Smith D L, Wood K V, McLaughlin J L. New cytotoxic Annonaceous acetogenins: bullatanocin and cis- and trans-bullatanocinone, from Annona bullata (Annonaceae).  Tetrahedron. 1993;  49 747-754
  • 46 Gu Z M, Fang X P, Zeng L, Wood K V, McLaughlin J L. Bullacin: a new cytotoxic Annonaceous acetogenin from Annona bullata.  Heterocycles. 1993;  36 2221-2228
  • 47 Zafra-Polo M C, Figadere B, Gallardo T, Tormo J R, Cortes D. Natural acetogenins from Annonaceae, synthesis and mechanisms of action.  Phytochemistry. 1998;  48 1087-1117
  • 48 Rieser M J, Kozlowski J F, Wood K V, McLaughlin J L. Muricatacin: a simple biologically active acetogenin derivative from the seeds of Annona muricata (Annonaceae).  Tetrahedron Lett. 1991;  32 1137-1140
  • 49 Rieser M J, Hui Y H, Rupprecht J K, Kozlowski J F, Wood K V, McLaughlin J L, Hanson P R, Zhuang Z, Hoye T R. Determination of absolute configuration of stereogenic carbinol centers in Annonaceous acetogenins by proton and fluorine-19 NMR analysis of Mosher ester derivatives.  J Am Chem Soc. 1992;  114 10203-10213
  • 50 Fujimoto Y, Murasaki C, Shimada H, Nishioka S, Kakinuma K, Singh S, Singh M, Gupta Y K, Sahai M. Annonaceous acetogenins from the seeds of Annona squamosa. Non-adjacent bis-tetrahydrofuranic acetogenins.  Chem Pharm Bull. 1994;  42 1175-1184
  • 51 Yu J G, Hu X E, Ho D K, Bean M F, Stephens R E, Cassady J M, Brinen L S, Clardy J. Absolute stereochemistry of (+)-gigantecin from Annona coriacea (Annonaceae).  J Org Chem. 2002;  59 1598-1599
  • 52 Duret P, Laurens A, Hocquemiller R, Cortex D, Cave A. Acetogenins of Annonaceae. 34. Isoacetogenins, artifacts issued from translacationization from annonaceous acetogenins.  Heterocycles. 1994;  39 741-749
  • 53 Duret P, Figadere B, Hocquemiller R, Cave A. Epimerization of Annonaceous acetogenins under basic conditions.  Tetrahedron Lett. 1997;  38 8849-8852
  • 54 Hopp D C, Conway W D, McLaughlin J L. Using countercurrent chromatography to assist in the purification of new Annonaceous acetogenins from Annona squamosa.  Phytochem Anal. 1999;  10 339-347
  • 55 Duret P, Waechter A I, Margraff R, Foucault A, Hocquemiller R, Cave A. High-speed countercurrent chromatography: a promising method for the separation of the Annonaceous acetogenins.  J Liq Chromatogr Relat Technol. 1997;  20 627-635
  • 56 Duret P, Waechter A-I, Figadere B, Hocquemiller R, Cave A. Determination of absolute configurations of carbinols of Annonaceous acetogenins with 2-naphthylmethoxyacetic acid esters.  J Org Chem. 1998;  63 4717-4720
  • 57 Hirayama K, Akashi S, Yuji R, Niitsu U, Fujimoto Y. Structural studies of polyhydroxybis(tetrahydrofuran) acetogenins from Annona squamosa using the combination of chemical derivatization and precursor-ion scanning mass spectrometry.  Org Mass Spectrom. 1993;  28 1516-1524
  • 58 Gu Z M, Zhou D, Wu J, Shi G, Zeng L, McLaughlin J L. Screening for Annonaceous acetogenins in bioactive plant extracts by liquid chromatography/mass spectrometry.  J Nat Prod. 1997;  60 242-248
  • 59 Chang F R, Wu Y C. Novel cytotoxic Annonaceous acetogenins from Annona muricata.  J Nat Prod. 2001;  64 925-931
  • 60 Chang F R, Liaw C C, Lin C Y, Chou C J, Chiu H F, Wu Y C. New adjacent bis-tetrahydrofuran Annonaceous acetogenins from Annona muricata.  Planta Med. 2003;  69 241-246
  • 61 Liaw C C, Chang F R, Wu C C, Chen S L, Bastow Kenneth F, Hayashi K I, Nozaki H, Lee K H, Wu Y C. Nine new cytotoxic monotetrahydrofuranic Annonaceous acetogenins from Annona montana.  Planta Med. 2004;  70 948-959
  • 62 Liaw C C, Chang F R, Wu M J, Wu Y C. A novel constituent from Rollinia mucosa, rollicosin, and a new approach to develop Annonaceous acetogenins as potential antitumor agents.  J Nat Prod. 2003;  66 279-281
  • 63 Xie H H, Wei X Y, Wang J D, Liu M F, Yang R Z. A new cytotoxic acetogenin from the seeds of Annona squamosa.  Chin Chem Lett. 2003;  14 588-590
  • 64 Wolvetang E J, Johnson K L, Krauer K, Ralph S J, Linnane A W. Mitochondrial respiratory chain inhibitors induce apoptosis.  FEBS Lett. 1994;  339 40-44
  • 65 Chih H W, Chiu H F, Tang K S, Chang F R, Wu Y C. Bullatacin, a potent antitumor Annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction.  Life Sci. 2001;  69 1321-1331
  • 66 Cartagena E, Colom O A, Neske A, Valdez J C, Bardon A. Effects of plant lactones on the production of biofilm of Pseudomonas aeruginosa.  Chem Pharm Bull. 2007;  55 22-25
  • 67 Ahammadsahib K I, Hollingworth R M, McGovren J P, Hui Y H, McLaughlin J L. Mode of action of bullatacin: a potent antitumor and pesticidal Anonaceous acetogenin.  Life Sci. 1993;  53 1113-1120
  • 68 Degli Esposti M, Ghelli A, Ratta M, Cortes D, Estornell E. Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (complex I).  Biochem J. 1994;  301 161-167
  • 69 Oberlies N H, Jones J L, Corbett T H, Fotopoulos S S, McLaughlin J L. Tumor cell growth inhibition by several Anonaceous acetogenins in an in vitro disk diffusion assay.  Cancer Lett. 1995;  96 55-62
  • 70 Oberlies N H, Croy V L, Harrison M L, McLaughlin J L. The Anonaceous acetogenin bullatacin is cytotoxic against multidrug-resistant human mammary adenocarcinoma cells.  Cancer Lett. 1997;  115 73-79
  • 71 Shimada H, Grutzner J B, Kozlowski J F, McLaughlin J L. Membrane conformations and their relation to cytotoxicity of asimicin and its analogs.  Biochemistry. 1998;  37 854-866
  • 72 Kuwabara K, Takada M, Iwata J, Tatsumoto K, Sakamoto K, Iwamura H, Miyoshi H. Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimics.  Eur J Biochem. 2000;  267 2538-2546
  • 73 Yuan S S F, Chang H L, Chen H W, Yeh Y T, Kao Y H, Lin K H, Wu Y C, Su J H. Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway.  Life Sci. 2003;  72 2853-2861
  • 74 Yuan S S F, Chang H L, Chen H W, Kuo F C, Liaw C C, Su J H, Wu Y C. Selective cytotoxicity of squamocin on T24 bladder cancer cells at the S-phase via a Bax-, Bad-, and caspase-3-related pathways.  Life Sci. 2006;  78 869-874
  • 75 Lu M C, Yang S H, Hwang S L, Lu Y J, Lin Y H, Wang S R, Wu Y C, Lin S R. Induction of G2/M phase arrest by squamocin in chronic myeloid leukemia (K562) cells.  Life Sci. 2006;  78 2378-2383
  • 76 Rupprecht J K, Chang C J, Cassady J M, McLaughlin J L, Mikolajczak K L, Weisleder D. Asimicin, a new cytotoxic and pesticidal acetogenin from the pawpaw, Asimina triloba (Annonaceae).  Heterocycles. 1986;  24 1197-1201
  • 77 Ratnayake S, Rupprecht J K, Potter W M, McLaughlin J L. Evaluation of various parts of the paw paw tree, Asimina triloba (Annonaceae), as commercial sources of the pesticidal Anonaceous acetogenins.  J Econ Entomol. 1992;  85 2353-2356
  • 78 He K, Zeng L, Ye Q, Shi G, Oberlies N H, Zhao G X, Njoku C J, McLaughlin J L. Comparative structure-activity relationship evaluations of Anonaceous acetogenins for pesticidal activity.  Pestic Sci. 1997;  49 372-378
  • 79 Alali F Q, Kaakeh W, Bennett G W, McLaughlin J L. Annonaceous acetogenins as natural pesticides: potent toxicity against insecticide-susceptible and -resistant German cockroaches (Dictyoptera: Blattellidae).  J Econ Entomol. 1998;  91 641-649
  • 80 Ohsawa K, Atsuzawa S, Mitsui T, Yamamoto I. Isolation and insecticidal activity of three acetogenins from seeds of pond apple, Annona glabra L.  Nippon Noyaku Gakkaishi. 1991;  16 93-96
  • 81 Guadano A, Gutierrez C, De la Pena E, Cortes D, Gonzalez-Coloma A. Insecticidal and mutagenic evaluation of two Anonaceous acetogenins.  J Nat Prod. 2000;  63 773-776
  • 82 Lewis M A, Arnason J T, Philogene B J R, Rupprecht J K, McLaughlin J L. Inhibition of respiration at site I by asimicin, an insecticidal acetogenin of the pawpaw, Asimina triloba (Annonaceae).  Pestic Biochem Physiol. 1993;  45 15-23
  • 83 Friedrich T, Ohnishi T, Forche E, Kunze B, Jansen R, Trowitzsch W, Hoefle G, Reichenbach H, Weiss H. Two binding sites for naturally occurring inhibitors in mitochondrial and bacterial NADH : ubiquinone oxidoreductase (complex I).  Biochem Soc Trans. 1994;  22 226-230
  • 84 Hollingworth R M, Ahammadsahib K I, Gadelhak G, McLaughlin J L. New inhibitors of complex I of the mitochondrial electron transport chain with activity as pesticides.  Biochem Soc Trans. 1994;  22 230-233
  • 85 Miyoshi H, Ohshima M, Shimada H, Akagi T, Iwamura H, McLaughlin J L. Essential structural factors of Annonaceous acetogenins as potent inhibitors of mitochondrial complex I.  Biochim Biophys Acta. 1998;  1365 443-452
  • 86 Miyoshi H. Inhibitors of mitochondrial respiratory enzymes.  J Pestic Sci. 2005;  30 120-121
  • 87 Takada M, Kuwabara K, Nakato H, Tanaka A, Iwamura H, Miyoshi H. Definition of crucial structural factors of acetogenins, potent inhibitors of mitochondrial complex I.  Biochim Biophys Acta. 2000;  1460 302-310
  • 88 Murai M, Ichimaru N, Abe M, Nishioka T, Miyoshi H. Synthesis of photolabile Δlac-acetogenin for photoaffinity labeling of mitochondrial complex I.  J Pestic Sci. 2006;  31 156-158
  • 89 Ichimaru N, Yoshinaga N, Nishioka T, Miyoshi H. Effect of stereochemistry of Δlac-acetogenins on the inhibition of mitochondrial complex I (NADH-ubiquinone oxidoreductase).  Tetrahedron. 2007;  63 1127-1139
  • 90 Myint S H, Laurens A, Hocquemiller R, Cave A, Davoust D, Cortes D. Murisolin: a new cytotoxic mono-tetrahydrofuran-γ-lactone from Annona muricata.  Heterocycles. 1990;  31 861-867
  • 91 Hattori Y, Kimura Y, Moroda A, Konno H, Abe M, Miyoshi H, Goto T, Makabe H. Synthesis of murisolin, (15R,16R,19R,20S)-murisolin A, and (15R,16R,19S,20S)-16,19-cis-murisolin and their inhibitory action with bovine heart mitochondrial complex I.  Chem Asian J. 2006;  1 894-904
  • 92 Ye Q, Zeng L, Zhang Y, Zhao G X, McLaughlin J L, Woo M H, Evert D R. Longicin and goniothalamicinone: novel bioactive monotetrahydrofuran acetogenins from Asimina longifolia.  J Nat Prod. 1995;  58 1398-1406
  • 93 Hanessian S, Giroux S, Buffat M. Total synthesis and structural confirmation of (+)-longicin.  Org Lett. 2005;  7 3989-3992
  • 94 Gleye C, Duret P, Laurens A, Hocquemiller R, Cave A. cis-Monotetrahydrofuran acetogenins from the roots of Annona muricata.  J Nat Prod. 1998;  61 576-579
  • 95 Goksel H, Stark C B W. Total synthesis of cis-solamin: exploiting the RuO4-catalyzed oxidative cyclization of dienes.  Org Lett. 2006;  8 3433-3436
  • 96 Zhao H, Gorman J S T, Pagenkopf B L. Advances in Lewis acid controlled carbon-carbon bond-forming reactions enable a concise and convergent total synthesis of bullatacin.  Org Lett. 2006;  8 4379-4382
  • 97 Keum G, Hwang C H, Kang S B, Kim Y, Lee E. Stereoselective syntheses of rolliniastatin 1, rollimembrin, and membranacin.  J Am Chem Soc. 2005;  127 10396-10399
  • 98 Gonzalez M C, Tormo J R, Bermejo A, Zafra-Polo M C, Estornell E, Cortes D. Rollimembrin, a novel acetogenin inhibitor of mammalian mitochondrial complex I.  Bioorg Med Chem Lett. 1997;  7 1113-1118
  • 99 He K, Shi G, Zhao G X, Ye Q, Schwedler J T, Wood K V, McLaughlin J L. Three new adjacent bis-tetrahydrofuran acetogenins with four hydroxyl groups from Asimina triloba.  J Nat Prod. 1996;  59 1029-1034
  • 100 Nattrass G L, Diez E, McLachlan M M, Dixon D J, Ley S V. The total synthesis of the Annonaceous acetogenin 10-hydroxyasimicin.  Angew Chem Int Ed Engl. 2005;  44 580-584
  • 101 Saez J, Sahpaz S, Villaescusa L, Hocquemiller R, Cave A, Cortes D. Acetogenins of the Annonaceae. 18. Rioclarin and membranacin, two new bis-tetrahydrofuran acetogenins of the seeds of Rollinia membranacea.  J Nat Prod. 1993;  56 351-356
  • 102 Marshall J A, Sabatini J J. An outside-in approach to adjacent bistetrahydrofuran Annonaceous acetogenins with C 2 core symmetry. Total synthesis of asimicin and a C32 analogue.  Org Lett. 2006;  8 3557-3560
  • 103 Ye Q, He K, Oberlies N H, Zeng L, Shi G, Evert D, McLaughlin J L. Longimicins A – D: novel bioactive acetogenins from Asimina longifolia (Annonaceae) and structure-activity relationships of asimicin type of annonaceous acetogenins.  J Med Chem. 1996;  39 1790-1796
  • 104 Tominaga H, Maezaki N, Yanai M, Kojima N, Urabe D, Ueki R, Tanaka T. First total synthesis of longimicin D.  Eur J Org Chem. 2006;  2006 1422-1429
  • 105 Shi G, Kozlowski J F, Schwedler J T, Wood K V, MacDougal J M, McLaughlin J L. Muconin and mucoxin: additional nonclassical bioactive acetogenins from Rollinia mucosa.  J Org Chem. 1996;  61 7988-7989
  • 106 Narayan R S, Borhan B. Synthesis of the proposed structure of mucoxin via regio- and stereoselective tetrahydrofuran ring-forming strategies.  J Org Chem. 2006;  71 1416-1429
  • 107 Shi G, Zheng L, Gu Z-M, MacDougal J M, McLaughlin J L. Absolute stereochemistries of sylvaticin and 12,15-cis-sylvaticin, bioactive C-20,23-cis nonadjacent bistetrahydrofuran Annonaceous acetogenins, from Rollinia mucosa.  Heterocycles. 1995;  41 1785-1796
  • 108 Donohoe T J, Harris R M, Burrows J, Parker J. Total synthesis of (+)-cis-sylvaticin: double oxidative cyclization reactions catalyzed by osmium.  J Am Chem Soc. 2006;  128 13704-13705
  • 109 Alkofahi A, Rupprecht J K, Liu Y M, Chang C J, Smith D L, McLaughlin J L. Gigantecin: a novel antimitotic and cytotoxic acetogenin, with nonadjacent tetrahydrofuran rings, from Goniothalamus giganteus (Annonaceae).  Experientia. 1990;  46 539-541
  • 110 Hoye T R, Eklov B M, Jeon J, Khoroosi M. Sequencing of three-component olefin metatheses: total synthesis of either (+)-gigantecin or (+)-14-deoxy-9-oxygigantecin.  Org Lett. 2006;  8 3383-3386
  • 111 Chavez D, Acevedo L A, Mata R. Jimenezin, a novel Annonaceous acetogenin from the seeds of Rollinia mucosa containing adjacent tetrahydrofuran-tetrahydropyran ring systems.  J Nat Prod. 1998;  61 419-421
  • 112 Bandur N G, Bruckner D, Hoffmann R W, Koert U. Total synthesis of jimenezin via an intramolecular allylboration.  Org Lett. 2006;  8 3829-3831
  • 113 Shi G, Alfonso D, Fatope M O, Zeng L, Gu Z M, Zhao G X, He K, MacDougal J M, McLaughlin J L. Mucocin: a new Annonaceous acetogenin bearing a tetrahydropyran ring.  J Am Chem Soc. 1995;  117 10409-10410
  • 114 Crimmins M T, Zhang Y, Diaz F A. Total synthesis of (−)-mucocin.  Org Lett. 2006;  8 2369-2372
  • 115 Alali F Q, Rogers L, Zhang Y, McLaughlin J L. Unusual bioactive Annonaceous acetogenins from Goniothalamus giganteus.  Tetrahedron. 1998;  54 5833-5844
  • 116 Strand D, Rein T. Total synthesis of pyranicin.  Org Lett. 2004;  7 199-202
  • 117 Strand D, Rein T. Synthesis of pyragonicin.  Org Lett. 2005;  7 2779-2781
  • 118 Takahashi S, Ogawa N, Koshino H, Nakata T. Total synthesis of the proposed structure for pyragonicin.  Org Lett. 2005;  7 2783-2786
  • 119 Quinn K J, Isaacs A K, DeChristopher B A, Szklarz S C, Arvary R A. Asymmetric total synthesis of rollicosin.  Org Lett. 2005;  7 1243-1245
  • 120 Makabe H, Kimura Y, Higuchi M, Konno H, Murai M, Miyoshi H. Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin, squamostolide, and their inhibitory action with bovine heart mitochondrial complex I.  Bioorg Med Chem. 2006;  14 3119-3130
  • 121 Hoppen S, Emde U, Friedrich T, Grubert L, Koert U. Natural-product hybrids: design, synthesis, and biological evaluation of quinone-Annonaceous acetogenins.  Angew Chem Int Ed Engl. 2000;  39 2099-2102
  • 122 Arndt S, Emde U, Baurle S, Friedrich T, Grubert L, Koert U. Quinone-Annonaceous acetogenins: synthesis and complex I inhibition studies of a new class of natural product hybrids.  Chem Eur J. 2001;  7 993-1005
  • 123 Duval R, Lewin G, Hocquemiller R. Semisynthesis of heterocyclic analogues of squamocin, a cytotoxic annonaceous acetogenin, by an unusual oxidative decarboxylation reaction.  Bioorg Med Chem. 2003;  11 3439-3446
  • 124 Duval R A, Lewin G, Peris E, Chahboune N, Garofano A, Droese S, Cortes D, Brandt U, Hocquemiller R. Heterocyclic analogues of squamocin as inhibitors of mitochondrial complex I. On the role of the terminal lactone of Annonaceous acetogenins.  Biochemistry. 2006;  45 2721-2728
  • 125 Duval R A, Poupon E, Romero V, Peris E, Lewin G, Cortes D, Brandt U, Hocquemiller R. Analogues of cytotoxic squamocin using reliable reactions: new insights into the reactivity and role of the α,β-unsaturated lactone of the Annonaceous acetogenins.  Tetrahedron. 2006;  62 6248-6257
  • 126 Kojima N, Fushimi T, Maezaki N, Tanaka T, Yamori T. Synthesis of hybrid acetogenins, α,β-unsaturated-γ-lactone-free nitrogen-containing heterocyclic analogues, and their cytotoxicity against human cancer cell lines.  Bioorg Med Chem Lett. 2008;  18 1637-1641
  • 127 Zeng B B, Wu Y, Yu Q, Wu Y L, Li Y, Chen X G. Enantiopure simple analogues of Annonaceous acetogenins with remarkable selective cytotoxicity towards tumor cell lines.  Angew Chem Int Ed. 2000;  39 1934-1937
  • 128 Rodier S, Le Huerou Y, Renoux B, Doyon J, Renard P, Pierre A, Gesson J P, Gree R. Synthesis and cytotoxic activity of acetogenin analogues.  Bioorg Med Chem Lett. 2000;  10 1373-1375
  • 129 Yao Z J, Wu H P, Wu Y L. Polyether mimics of naturally occurring cytotoxic Annonaceous acetogenins.  J Med Chem. 2000;  43 2484-2487
  • 130 Jiang S, Liu Z H, Sheng G, Zeng B B, Cheng X G, Wu Y L, Yao Z J. Mimicry of Annonaceous acetogenins: enantioselective synthesis of a (4R)-hydroxy analogue having potent antitumor activity.  J Org Chem. 2002;  67 3404-3408
  • 131 Zeng B B, Wu Y, Jiang S, Yu Q, Yao Z J, Liu Z H, Li H Y, Li Y, Chen X G, Wu Y L. Studies on mimicry of naturally occurring Annonaceous acetogenins: non-THF analogues leading to remarkable selective cytotoxicity against human tumor cells.  Chem Eur J. 2003;  9 282-290
  • 132 Rodier S, Le Huerou Y, Renoux B, Doyon J, Renard P, Pierre A, Gesson J P, Gree R. New cytotoxic analogues of Annonaceous acetogenins.  Anticancer Drug Des. 2001;  16 109-117
  • 133 Fujita D, Ichimaru N, Abe M, Murai M, Hamada T, Nishioka T, Miyoshi H. Synthesis of non-THF analogs of acetogenin toward simplified mimics.  Tetrahedron Lett. 2005;  46 5775-5779
  • 134 Liu H X, Huang G R, Zhang H M, Wu J R, Yao Z J. Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity against cancer cells.  Bioorg Med Chem Lett. 2007;  17 3426-3430
  • 135 Liu H X, Shao F, Li G Q, Xun G L, Yao Z J. Tuning the acyclic ether moiety of anticancer agent AA005 with conformationally constrained fragments.  Chem Eur J. 2008;  14 8632-8639
  • 136 Ye Q, Shi G, He K, McLaughlin J L. Chlorinated Annonaceous acetogenins and their bioactivities.  J Nat Prod. 1996;  59 994-996
  • 137 Kojima N, Hayashi H, Suzuki S, Tominaga H, Maezaki N, Tanaka T, Yamori T. Synthesis of C4-fluorinated solamins and their growth inhibitory activity against human cancer cell lines.  Bioorg Med Chem Lett. 2008;  18 6451-6453
  • 138 Gallardo T, Saez J, Granados H, Tormo J R, Velez I D, Brun N, Torres B, Cortes D. 10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I.  J Nat Prod. 1998;  61 1001-1005
  • 139 Duret P, Hocquemiller R, Gantier J C, Figadere B. Semisynthesis and cytotoxicity of amino acetogenins and derivatives.  Bioorg Med Chem. 1999;  7 1821-1826
  • 140 Derbre S, Roue G, Poupon E, Susin Santos A, Hocquemiller R. Annonaceous acetogenins: the hydroxyl groups and THF rings are crucial structural elements for targeting the mitochondria, demonstration with the synthesis of fluorescent squamocin analogues.  Chembiochem. 2005;  6 979-982
  • 141 Alexander M D, Burkart M D, Leonard M S, Portonovo P, Liang B, Ding X, Joullie M M, Gulledge B M, Aggen J B, Chamberlin A R, Sandler J, Fenical W, Cui J, Gharpure S J, Polosukhin A, Zhang H R, Evans P A, Richardson A D, Harper M K, Ireland C M, Vong B G, Brady T P, Theodorakis E A, La Clair J J. A central strategy for converting natural products into fluorescent probes.  Chembiochem. 2006;  7 409-416
  • 142 Maezaki N, Urabe D, Yano M, Tominaga H, Morioka T, Kojima N, Tanaka T. Synthesis of fluorescent solamin for visualization of cell distribution.  Heterocycles. 2007;  73 159-164
  • 143 Kojima N, Morioka T, Yano M, Suga Y, Maezaki N, Tanaka T. Convergent synthesis of fluorescence labeled solamin.  Heterocycles. 2009;  79 387-393
  • 144 Liu H X, Huang G R, Zhang H M, Jiang S, Wu J R, Yao Z J. A structure-activity guided strategy for fluorescent labeling of Annonaceous acetogenin mimetics and their application in cell biology.  Chembiochem. 2007;  8 172-177
  • 145 Zafra-Polo M C, Gonzalez M C, Estornell E, Sahpaz S, Cortes D. Acetogenins from Annonaceae, inhibitors of mitochondrial complex I.  Phytochemistry. 1996;  42 253-271
  • 146 Sasaki S, Naito H, Maruta K, Kawahara E, Maeda M. Novel calcium ionophores: supramolecular complexation by the hydroxylated-bistetrahydrofuran skeleton of potent antitumor annocnaceous acetogenins.  Tetrahedron Lett. 1994;  35 3337-3340
  • 147 Araya H, Fujimoto Y, Hirayama K. Structural elucidation of tetrahydrofuranic acetogenins by means of precursor-ion scanning method.  Yuki Gosei Kagaku Kyokaishi. 1994;  52 765-777
  • 148 Sasaki S, Maruta K, Naito H, Sugihara H, Hiratani K, Maeda M. New calcium-selective electrodes based on Annonaceous acetogenins and their analogs with neighboring bistetrahydrofuran.  Tetrahedron Lett. 1995;  36 5571-5574
  • 149 Sasaki S, Maruta K, Naito H, Maemura R, Kawahara E, Maeda M. Novel acyclic ligands for metal cations based on the adjacent bistetrahydrofuran as analogs of natural Annonaceous acetogenins.  Tetrahedron. 1998;  54 2401-2410
  • 150 Peyrat J F, Mahuteau J, Figadere B, Cave A. NMR studies of Ca2+ complexes of Annonaceous acetogenins.  J Org Chem. 1997;  62 4811-4815
  • 151 Wu S N, Chiang H T, Chang F R, Liaw C C, Wu Y C. Stimulatory effects of squamocin, an Annonaceous acetogenin, on Ca2+-activated K+ current in cultured smooth muscle cells of human coronary artery.  Chem Res Toxicol. 2003;  16 15-22
  • 152 Liaw C C, Yang Y L, Chen M, Chang F R, Chen S L, Wu S H, Wu Y C. Mono-tetrahydrofuran Annonaceous acetogenins from Annona squamosa as cytotoxic agents and calcium ion chelators.  J Nat Prod. 2008;  71 764-771
  • 153 Gu Z M, Zhou D, Lewis N J, Wu J, Johnson H A, McLaughlin J L, Gordon J. Quantitative evaluation of Annonaceous acetogenins in monthly samples of paw paw (Asimina triloba) twigs by liquid chromatography/electrospray ionization/tandem mass spectrometry.  Phytochem Anal. 1999;  10 32-38
  • 154 McLaughlin J L. Paw paw and cancer: Annonaceous acetogenins from discovery to commercial products.  J Nat Prod. 2008;  71 1311-1321
  • 155 Cuendet M, Oteham C P, Moon R C, Keller W J, Peaden P A, Pezzuto J M. Dietary administration of Asimina triloba (Paw Paw) extract increases tumor latency in N-methyl-N-nitrosourea-treated rats.  Pharm Biol. 2008;  46 3-7
  • 156 Escobar-Khondiker M, Hoellerhage M, Muriel M P, Champy P, Bach A, Depienne C, Respondek G, Yamada E S, Lannuzel A, Yagi T, Hirsch Etienne C, Oertel W H, Jacob R, Michel P P, Ruberg M, Hoeglinger G U. Annonacin, a natural mitochondrial complex I inhibitor, causes Tau pathology in cultured neurons.  J Neurosci. 2007;  27 7827-7837

Dr. Yang-Chang Wu

Graduate Institute of Natural Products
Kaohsiung Medical University

100 Shih-Chuan 1st Road

703 Kaohsiung

Taiwan

Republic of China

Telefon: + 88 6 73 12 11 01ext. 21 97

Fax: + 88 6 73 11 47 73

eMail: yachwu@kmu.edu.tw