Journal of Applied Phycology

, Volume 22, Issue 5, pp 659–676 | Cite as

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery



A plethora of structurally novel bioactive secondary metabolites have been reported from the prokaryotic filamentous marine cyanobacteria in the past few decades. In addition to the production of harmful toxins, these marine blue-green algae are emerging as an important source of anticancer drugs. The majority of these potent biomolecules, including the dolastatins, curacin A, hectochlorin, the apratoxins, and the lyngbyabellins, belongs to the mixed polyketide–polypeptide structural class. Furthermore, a high proportion of these natural products target eukaryotic cytoskeleton, such as tubulin and actin microfilaments, making them an attractive source of potential anticancer drugs. In recent years, a number of potent marine cyanobacteria have also been reported to modulate cell death and apoptosis in cancer cells as well as target enzymes such as histone deacetylase. A number of marine cyanobacterial compounds have also served as structural templates for the generation of new drug leads, further attesting to the importance of these marine microbes as an important source of new pharmaceuticals. This review serves to highlight the chemistry and biology of selected anticancer marine cyanobacterial natural products exhibiting significant biological activities in the nanomolar or submicromolar range, and their discussion will be based on the different modes of action.


Marine cyanobacteria Drug discovery Anticancer Natural products 


  1. Akashi Y, Okamoto I, Suzuki M, Tamura K, Iwasa T, Hisada S, Satoh T, Nakagawa K, Ono K, Fukuoka M (2007) The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo. Br J Cancer 96:1532–1539PubMedCrossRefGoogle Scholar
  2. Ali MA, Bates RB, Crane ZD, Dicus CW, Gramme MR, Hamel E, Marcischak J, Martinez DS, McClure KJ, Nakkiew P, Pettit GR, Stessman CC, Sufi BA, Yarick GV (2005) Dolastatin 11 conformations, analogues and pharmacophore. Bioorg Med Chem 13:4138–4152PubMedCrossRefGoogle Scholar
  3. Aráoz R, Molgó J, Tandeau de Marsac N (2010) Neurotoxic cyanobacterial toxins. Toxicon (in press)Google Scholar
  4. Bai R, Verdier-Pinard P, Gangwar S, Stessman CC, McClure KJ, Sausville EA, Pettit GR, Hamel E (2001) Dolastatin 11, a marine depsipeptide, arrests cells at cytokinesis and induces hyperpolymerization of purified actin. Mol Pharmacol 59:462–469PubMedGoogle Scholar
  5. Barrios-Llerena ME, Burja AM, Wright PC (2007) Genetic analysis of polyketide synthase and peptide synthetase genes in cyanobacteria as a mining tool for secondary metabolites. J Ind Microbiol Biotechnol 34:443–456PubMedCrossRefGoogle Scholar
  6. Bonnard I, Rolland M, Francisco C, Banaigs B (1997) Total structure and biological properties of laxaphycins A and B, cyclic lipopeptides from the marine cyanobacterium Lyngbya majuscula. Lett Pept Sci 4:289–292Google Scholar
  7. Bonnard I, Rolland M, Salmon J-M, Debiton E, Barthomeuf C, Banaigs B (2007) Total structure and inhibition of tumor cell proliferation of laxaphycins. J Med Chem 50:1266–1279PubMedCrossRefGoogle Scholar
  8. Bowers A, West N, Taunton J, Schreiber SL, Bradner JE, Williams RM (2008) Total synthesis and biological mode of action of largazole: a potent class I histone deacetylase inhibitor. J Am Chem Soc 130:11219–11222PubMedCrossRefGoogle Scholar
  9. Bowers AA, West N, Newkirk TL, Troutman-Youngman AE, Schreiber SL, Wiest O, Bradner JE, Williams RM (2009a) Synthesis and histone deacetylase inhibitory activity of largazole analogs: alteration of the zinc-binding domain and macrocyclic scaffold. Org Lett 11:1301–1304PubMedCrossRefGoogle Scholar
  10. Bowers AA, Greshock TJ, West N, Estiu G, Schreiber SL, Wiest O, Williams RM, Bradner JE (2009b) Synthesis and conformation–activity relationships of the peptide isosteres of FK228 and largazole. J Am Chem Soc 131:2900–2905PubMedCrossRefGoogle Scholar
  11. Chen J, Forsyth CJ (2003a) Total synthesis of apratoxin A. J Am Chem Soc 125:8734–8735PubMedCrossRefGoogle Scholar
  12. Chen J, Forsyth CJ (2003b) Synthesis of the apratoxin 2,4-disubstituted thiazoline via an intramolecular Aza-Wittig reaction. Org Lett 8:1281–1283CrossRefGoogle Scholar
  13. Chen J, Forsyth CJ (2004) Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A. Proc Natl Acad Sci USA 101:12067–12072PubMedCrossRefGoogle Scholar
  14. Chen F, Gao A-H, Li J, Nan F-J (2009) Synthesis and biological evaluation of C7-demethyl largazole analogues. ChemMedChem 4:1269–1272PubMedCrossRefGoogle Scholar
  15. Cunningham C, Appleman LJ, Kirvan-Visovatti M, Ryan DP, Regan E, Vukelja S, Bonate PL, Ruvuna F, Fram RJ, Jekunen A, Weitman S, Hammond LA, Eder JP (2005) Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 11:7825–7833PubMedCrossRefGoogle Scholar
  16. Dai L, Zhang H, Tan W, Xu Z, Ye T (2008) Total synthesis of largazole. Synlett 15:2379–2383Google Scholar
  17. Doi T, Numajiri Y, Munakata A, Takahashi T (2006) Total synthesis of apratoxin A. Org Lett 8:531–534PubMedCrossRefGoogle Scholar
  18. de Jonge MJ, van der Gaast A, Planting AS, van Doorn L, Lems A, Boot I, Wanders J, Satomi M, Verweij J (2005) Phase I and pharmacokinetic study of the dolastatin 10 analogue TZT-1027, given on days 1 and 8 of a 3-week cycle in patients with advanced solid tumors. Clin Cancer Res 11:3806–3813PubMedCrossRefGoogle Scholar
  19. Ebbinghaus S, Rubin E, Hersh E, Cranmer LD, Bonate PL, Fram RJ, Jekunen A, Weitman S, Hammond LA (2005) A phase I study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously daily for 5 consecutive days every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 11:7807–7816PubMedCrossRefGoogle Scholar
  20. Frankmolle WP, Knubel G, Moore RE, Patterson GML (1992) Antifungal cyclic peptides from the terrestrial blue-green alga Anabeana laxa. 2. Structures of laxaphycins A, B, C, D, and E. J Antibiot 45:1458–1466PubMedGoogle Scholar
  21. Gerwick WH, Mrozek C, Moghaddam MF, Agarwal SK (1989) Novel cytotoxic peptides from the tropical marine cyanobacterium Hormothamnion enteromorphoides. 1. Discovery, isolation and initial chemical and biological characterization of the hormothamnins from wild and cultured material. Experientia 45:115–121PubMedCrossRefGoogle Scholar
  22. Gerwick WH, Proteau PJ, Nagle DG, Hamel E, Blokhin A, Slate DL (1994) Structure of curacin A, a novel antimitotic, antiproliferative, and brine shrimp toxic natural product from the marine cyanobacterium Lyngbya majuscula. J Org Chem 59:1243–1245CrossRefGoogle Scholar
  23. Gerwick WH, Tan LT, Sitachitta N (2001) Nitrogen-containing metabolites from marine cyanobacteria. In: Cordell GA (ed) The alkaloids: chemistry and biology, vol 57. Academic, San Diego, pp 75–184Google Scholar
  24. Gerwick WH, Coates RC, Engene N, Gerwick L, Grindberg RV, Jones AC, Sorrels CM (2008) Giant marine cyanobacteria produce exciting potential pharmaceuticals. Microbe 3:277–284Google Scholar
  25. Ghosh AK, Kulkarni S (2008) Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase. Org Lett 10:3907–3909PubMedCrossRefGoogle Scholar
  26. Gilles A, Martinez J, Cavelier F (2009) Supported synthesis of oxoapratoxin A. J Org Chem 74:4298–4304PubMedCrossRefGoogle Scholar
  27. Greystoke A, Blagden S, Thomas AL, Scott E, Attard G, Molife R, Vidal L, Pacey S, Sarkar D, Jenner A, De-Bono JS, Steward W (2006) A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours. Ann Oncol 17:1313–1319PubMedCrossRefGoogle Scholar
  28. Gutierrez M, Suyama TL, Engene N, Wingerd JS, Matainaho T, Gerwick WH (2008) Apratoxin D, a potent cytotoxic cyclodepsipeptide from Papua New Guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida. J Nat Prod 71:1099–1103PubMedCrossRefGoogle Scholar
  29. Halkidou K, Gaughan L, Cook S, Leung HY, Neal DE, Robson CN (2004) Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate 59:177–189PubMedCrossRefGoogle Scholar
  30. Han B, McPhail KL, Gross H, Goeger DE, Mooberry SL, Gerwick WH (2005) Isolation and structure of five lyngbyabellin derivatives from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. Tetrahedron 61:11723–11729CrossRefGoogle Scholar
  31. Han B, Gross H, Goeger DE, Mooberry SL, Gerwick WH (2006) Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. J Nat Prod 69:572–575PubMedCrossRefGoogle Scholar
  32. Harrigan GG, Luesch H, Yoshida WY, Moore RE, Nagle DG, Paul VJ, Mooberry SL, Corbett TH, Valeriote FA (1998) Symplostatin 1: a dolastatin 10 analogue from the marine cyanobacterium Symploca hydnoides. J Nat Prod 61:1075–1077PubMedCrossRefGoogle Scholar
  33. Horgen FD, Kazmierski EB, Westenburg HE, Yoshida WY, Scheuer PJ (2002) Malevamide D: isolation and structure determination of an isodolastatin H analogue from the marine cyanobacterium Symploca hydroides. J Nat Prod 65:487–491PubMedCrossRefGoogle Scholar
  34. Horti J, Juhasz E, Monostori Z, Maeda K, Eckdardt S, Bodrogi I (2008) Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer. Can Chemother Pharmacol 62:173–180CrossRefGoogle Scholar
  35. Jones AC, Gu L, Sorrels CM, Sherman DH, Gerwick WH (2009) New tricks from ancient algae: natural products biosynthesis in marine cyanobacteria. Curr Opin Chem Biol 13:216–123PubMedCrossRefGoogle Scholar
  36. Jordan MA, Wilson L (1998) Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 10:123–130PubMedCrossRefGoogle Scholar
  37. Linington RG, Gonzalez J, Urena L, Romero LI, Ortega-Barria E, Gerwick WH (2007) Venturamides A and B: antimalarial constituents of the Panamanian marine cyanobacterium Oscillatoria sp. J Nat Prod 70:397–401PubMedCrossRefGoogle Scholar
  38. Linington RG, Edwards DJ, Shuman CF, McPhail KL, Matainaho T, Gerwick WH (2008) Symplocamide A, a potent cytotoxin and chymotrypsin inhibitor from the marine cyanobacterium Symploca sp. J Nat Prod 71:22–27PubMedCrossRefGoogle Scholar
  39. Linington RG, Clark BR, Trimble EE, Almanza A, Urena LD, Kyle DE, Gerwick WH (2009) Antimalarial peptides from marine cyanobacteria: isolation and structural elucidation of gallinamide A. J Nat Prod 72:14–17PubMedCrossRefGoogle Scholar
  40. Liu Y, Law BK, Luesch H (2009) Apratoxin A reversibly inhibits the secretory pathway by preventing cotranslational translocation. Mol Pharmacol 76:91–104PubMedCrossRefGoogle Scholar
  41. Luesch H, Yoshida WY, Moore RE, Paul VJ, Mooberry SL (2000) Isolation, structure determination, and biological activity of lyngbyabellin A from the marine cyanobacterium Lyngbya majuscula. J Nat Prod 63:611–615PubMedCrossRefGoogle Scholar
  42. Luesch H, Moore RE, Paul VJ, Mooberry SL, Corbett TH (2001a) Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J Nat Prod 64:907–910PubMedCrossRefGoogle Scholar
  43. Luesch H, Yoshida WY, Moore RE, Paul VJ, Corbett TH (2001b) Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula. J Am Chem Soc 123:5418–5423PubMedCrossRefGoogle Scholar
  44. Luesch H, Harrigan GG, Goetz G, Horgen FD (2002a) The cyanobacterial origin of potent anticancer agents originally isolated from sea hares. Curr Med Chem 9:1791–1806PubMedGoogle Scholar
  45. Luesch H, Yoshida WY, Moore RE, Paul VJ (2002b) New apratoxins of marine cyanobacterial origin from Guam and Palau. Bioorg Med Chem 10:1973–1978PubMedCrossRefGoogle Scholar
  46. Luesch H, Yoshida WY, Moore RE, Paul VJ, Mooberry SL, Corbett TH (2002c) Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452. J Nat Prod 65:16–20PubMedCrossRefGoogle Scholar
  47. Luesch H, Chanda SK, Raya RM, DeJesus PD, Orth AP, Walker JR, Izpisua Belmonte JC, Schultz PG (2006) A functional genomics approach to the mode of action of apratoxin A. Nat Chem Biol 2:158–167PubMedCrossRefGoogle Scholar
  48. Ma D, Zou B, Cai G, Hu X, Liu JO (2006) Total synthesis of the cyclodepsipeptide apratoxin A and its analogues and assessment of their biological activities. Chem Eur J 12:7615–7626CrossRefGoogle Scholar
  49. McPhail KL, Correa J, Linington RG, Gonzalez J, Ortega-Barria E, Capson TL, Gerwick WH (2007) Antimalarial linear lipopeptides from a Panamanian strain of the marine cyanobacterium Lyngbya majuscula. J Nat Prod 70:984–988PubMedCrossRefGoogle Scholar
  50. Marquez BL, Watts KS, Yokochi A, Roberts MA, Verdier-Pinard P, Jimenez JI, Hamel E, Scheuer PJ, Gerwick WH (2002) Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J Nat Prod 65:866–871PubMedCrossRefGoogle Scholar
  51. Matthew S, Ross C, Rocca JR, Paul VJ, Luesch H (2007) Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides. J Nat Prod 70:124–127PubMedCrossRefGoogle Scholar
  52. Matthew S, Schupp PJ, Luesch H (2008a) Apratoxin E, a cytotoxic peptolide from a Guamanian collection of the marine cyanobacterium Lyngbya bouillonii. J Nat Prod 71:1113–1116PubMedCrossRefGoogle Scholar
  53. Matthew S, Ross C, Paul VJ, Luesch H (2008b) Pompenopeptins A and B, new cyclic peptides from the marine cyanobacterium Lyngbya confervoides. Tetrahedron 64:4081–4089CrossRefGoogle Scholar
  54. Matthew S, Paul VJ, Luesch H (2009) Largamides A-C, tiglic acid-containing cyclodepsipeptides with elastase-inhibitory activity from the marine cyanobacterium Lyngbya confervoides. Planta Med 75:528–533PubMedCrossRefGoogle Scholar
  55. Medina RA, Goeger DE, Hills P, Mooberry SL, Huang N, Romero LI, Ortega-Barria E, Gerwick WH, McPhail KL (2008) Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp. J Am Chem Soc 130:6324–6325PubMedCrossRefGoogle Scholar
  56. Mita AC, Hammond LA, Bonate PL, Weiss G, McCreery H, Syed S, Garrison M, Chu QSC, DeBono JS, Jones CB, Weitman S, Rowinsky EK (2006) Phase I and pharmacokinetic study of tasidotin hydrochloride (ILX651), a third-generation dolastatin-15 analogue, administered weekly for 3 weeks every 28 days in patients with advanced solid tumors. Clin Cancer Res 12:5207–5215PubMedCrossRefGoogle Scholar
  57. Mooberry SL, Leal RM, Tinley TL, Luesch H, Moore RE, Corbett TH (2003) The molecular pharmacology of symplostatin 1: a new antimitotic dolastatin 10 analog. Int J Cancer 104:512–521PubMedCrossRefGoogle Scholar
  58. Nakao Y, Yoshida WY, Takada Y, Kimura J, Yang L, Mooberry SL, Scheuer PJ (2004) Kulokekahilide-2, a cytotoxic depsipeptide from a cephalaspidean mollusk Philinopsis speciosa. J Nat Prod 67:1332–1340PubMedCrossRefGoogle Scholar
  59. Nasveschuk CG, Ungermannova D, Liu X, Phillips AJ (2008) A concise total synthesis of largazole, solution structure, and some preliminary structure activity relationships. Org Lett 10:3595–3598PubMedCrossRefGoogle Scholar
  60. Nogle LM, Gerwick WH (2002) Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage. Org Lett 4:1095–1098PubMedCrossRefGoogle Scholar
  61. Numajiri Y, Takahashi T, Doi T (2009) Total synthesis of (−)-apratoxin A, 34-epimer, and its oxazoline analogue. Chem Asian J 4:111–125PubMedCrossRefGoogle Scholar
  62. Oda T, Crane ZD, Dicus CW, Sufi BA, Bates RB (2003) Dolastatin 11 connects two long-pitch strands in F-actin to stabilize microfilaments. J Mol Biol 328:319–324PubMedCrossRefGoogle Scholar
  63. Patel S, Keohan ML, Saif MW, Rushing D, Baez L, Feit K, DeJager R, Anderson S (2006) Phase II study of intavenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy. Cancer 107:2881–2887PubMedCrossRefGoogle Scholar
  64. Pereira A, Cao Z, Murray TF, Gerwick WH (2009) Hoiamide A, a sodium channel activator of unusual architecture from a consortium of two Papua New Guinea cyanobacteria. Chem Biol 16:893–906PubMedCrossRefGoogle Scholar
  65. Plaza A, Bewley CA (2006) Largamides A–H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp. J Org Chem 71:6898–6907PubMedCrossRefGoogle Scholar
  66. Radau G (2000) Serine protease inhibiting cyanopeptides. Pharmazie 55:555–560PubMedGoogle Scholar
  67. Riely GJ, Gadgeel S, Rothman I, Saidman B, Sabbath K, Feit K, Kris MG, Rizvi NA (2007) A phase 2 study of TZT1027, administered weekly to patients with advanced non-small cell lung cancer following treatment with platinum-based chemotherapy. Lung Cancer 55:181–185PubMedCrossRefGoogle Scholar
  68. Risinger AL, Giles FJ, Mooberry SL (2009) Microtubule dynamics as a target in oncology. Cancer Treatment Rev 35:255–261CrossRefGoogle Scholar
  69. Schoffski P, Thate B, Beutel G, Bolte O, Otto D, Hofmann M, Ganser A, Jenner A, Cheverton P, Wanders J, Oguma T, Atsumi R, Satomi M (2004) Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer. Ann Oncol 15:671–679PubMedCrossRefGoogle Scholar
  70. Seiser T, Kamena F, Cramer N (2008) Synthesis and biological activity of largazole and derivatives. Angew Chem Int Ed 47:6483–6485CrossRefGoogle Scholar
  71. Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:1–10CrossRefGoogle Scholar
  72. Shen S, Zhang P, Lovchik MA, Li Y, Tang L, Chen Z, Zeng R, Ma D, Yuan J, Yu Q (2009) Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy. J Cell Biol 185:629–639PubMedCrossRefGoogle Scholar
  73. Simmons TL, McPhail KL, Ortega-Barria E, Mooberry SL, Gerwick WH (2006) Belamide A, a new antimitotic tetrapeptide from a Panamanian marine cyanobacterium. Tet Lett 47:3387–3390CrossRefGoogle Scholar
  74. Simmons TL, Gerwick WH (2008) Anticancer drugs of marine origin. In: Walsh P, Smith S, Fleming L, Solo-Gabriele H, Gerwick WH (eds) Oceans and human health: risks and remedies from the seas. Academic, New York, pp 431–452Google Scholar
  75. Simmons TL, Nogle LM, Media J, Valeriote FA, Mooberry SL, Gerwick WH (2009) Desmethoxymajusculamide C, a cyanobacterial depsipeptide with potent cytotoxicity in both cyclic and ring-opened forms. J Nat Prod 72:1011–1016PubMedCrossRefGoogle Scholar
  76. Soria-Mercado IE, Pereira A, Cao Z, Murray TF, Gerwick WH (2009) Alotamide A, a novel neuropharmacological agent from the marine cyanobacterium Lyngbya bouillonii. Org Lett 11:4704–4707PubMedCrossRefGoogle Scholar
  77. Suenaga K, Mutou T, Shibata T, Itoh T, Kigoshi H, Yamada K (1996) Isolation and stereostructure of aurilide, a novel cyclodepsipeptide from the Japanese sea hare Dolabella auricularia. Tet Lett 37:6771–6774CrossRefGoogle Scholar
  78. Suenaga K, Mutou T, Shibata T, Itoh T, Fujita T, Takada N, Hayamizu K, Takagi M, Irifune T, Kigoshi H, Yamada K (2004) Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity. Tetrahedron 60:8509–8527CrossRefGoogle Scholar
  79. Suenaga K, Kajiwara S, Kuribayashi S, Handa T, Kigoshi H (2008) Synthesis and cytotoxicity of aurilide analogs. Bioorg Med Chem Lett 18:3902–3905PubMedCrossRefGoogle Scholar
  80. Suyama TL, Gerwick WH (2008) Stereospecific total synthesis of somocystinamide A. Org Lett 10:4449–4452PubMedCrossRefGoogle Scholar
  81. Takada Y, Mori E, Umehara M, Nakao Y, Kimura J (2007) Reinvestigation of the stereochemistry of kulokekahilide-2. Tet Lett 48:7653–7656CrossRefGoogle Scholar
  82. Takada Y, Umehara M, Nakao Y, Kimura J (2008) Revised absolute stereochemistry of natural kulokekahilide-2. Tet Lett 49:1163–1165CrossRefGoogle Scholar
  83. Takahashi T, Nagamiya H, Doi T, Griffiths PG, Bray AM (2003) Solid phase library synthesis of cyclic depsipeptides: aurilide and aurilide analogues. J Comb Chem 5:414–428PubMedCrossRefGoogle Scholar
  84. Takahashi T, Takagi M, Shin-ya K, Doi T (2008) Total synthesis of largazole and its biological evaluation. Synlett 16:2483–2486Google Scholar
  85. Tamura K, Nakagawa K, Kurata T, Satoh T, Nogami T, Takeda K, Mitsuoka S, Yoshimura N, Kudoh S, Negoro S, Fukuoka M (2007) Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, which was administered to patients with advanced solid tumors on days 1 and 8 in 3-week courses. Cancer Chemother Pharmacol 60:285–293PubMedCrossRefGoogle Scholar
  86. Tan LT (2007) Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 68:954–979PubMedCrossRefGoogle Scholar
  87. Taniguchi M, Nunnery JK, Engene N, Esquenazi E, Byrum T, Dorrestein P, Gerwick WH (2010) Palmyramide A, a cyclic depsipeptide from a Palmyra atoll collection of the marine cyanobacterium Lyngbya majuscula. J Nat Prod (in press)Google Scholar
  88. Taori K, Matthew S, Rocca JR, Paul VJ, Luesch H (2007) Lyngbyastatins 5–7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp. J Nat Prod 70:1593–1600PubMedCrossRefGoogle Scholar
  89. Taori K, Paul VJ, Luesch H (2008a) Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp. J Am Chem Soc 130:1806–1807PubMedCrossRefGoogle Scholar
  90. Taori K, Paul VJ, Luesch H (2008b) Kempopetins A and B, serine protease inhibitors with different selectivity profiles from a marine cyanobacterium, Lyngbya sp. J Nat Prod 71:1625–1629PubMedCrossRefGoogle Scholar
  91. Taori K, Liu Y, Paul VJ, Luesch H (2009) Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole. ChemBioChem 10:1634–1639PubMedCrossRefGoogle Scholar
  92. Teruya T, Sasaki H, Fukazawa H, Suenaga K (2009) Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium Lyngbya sp.: isolation, stereostructure, and biological activity. Org Lett 11:5062–5065PubMedCrossRefGoogle Scholar
  93. Tidgewell K, Clark BR, Gerwick WH (2010) The natural products chemistry of cyanobacteria. In: Mander LN, Liu HW (eds) Comprehensive natural products chemistry II, vol 8. Pergamon (in press)Google Scholar
  94. Tripathi A, Puddick J, Prinsep MR, Lee PPF, Tan LT (2009) Hantupeptin A, a cytotoxic cyclic depsipeptide from a Singapore collection of Lyngbya majuscula. J Nat Prod 72:29–32PubMedCrossRefGoogle Scholar
  95. Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discovery 5:785–799CrossRefGoogle Scholar
  96. Umehara M, Takada Y, Nakao Y, Kimura J (2009) Intramolecular ester exchange of potent cytotoxic kulokekahilide-2. Tet Lett 50:840–843CrossRefGoogle Scholar
  97. Watanabe J, Natsume T, Kobayashi M (2007a) Comparison of the antivascular and cytotoxic activities of TZT-1027 (soblidotin) with those of other anticancer agents. Anticancer Drugs 18:905–911PubMedGoogle Scholar
  98. Watanabe J, Endo Y, Shimada N, Natsume T, Sasaki T, Kobayashi M (2007b) Antiangiogenic activity of TZT-1027 (soblidotin) on chick chorioallantoic membrane and human umbilical vein endothelial cells. In Vivo 21:297–304PubMedGoogle Scholar
  99. Williams PG, Yoshida WY, Quon MK, Moore RE, Paul VJ (2003) The structure of palau’amide, a potent cytotoxin from a species of the marine cyanobacterium Lyngbya. J Nat Prod 66:1545–1549PubMedCrossRefGoogle Scholar
  100. Wilson AJ, Byun D-S, Popova N, Murray LB, L’Italien K, Sowa Y, Arango D, Velcich A, Augenlicht LH, Mariadason JM (2006) Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem 281:13548–13558PubMedCrossRefGoogle Scholar
  101. Wipf P, Reeves JT, Balachandran R, Day BW (2002) Synthesis and biological evaluation of structurally highly modified analogues of the antimitotic natural product curacin A. J Med Chem 45:1901–1917PubMedCrossRefGoogle Scholar
  102. Wipf P, Reeves JT, Day BW (2004) Chemistry and biology of curacin A. Curr Pharm Design 10:1417–1437CrossRefGoogle Scholar
  103. Wrasidlo W, Mielgo A, Torres VA, Barbero S, Stoletov K, Suyama TL, Klemke RL, Gerwick WH, Carson DA, Stupack DG (2008) The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc Nat Acad Sci USA 105:2313–2318PubMedCrossRefGoogle Scholar
  104. Yamamoto N, Andoh M, Kawahara M, Fukuoka M, Niitani H (2009) Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeks. Cancer Sci 100:316–321CrossRefGoogle Scholar
  105. Ying Y, Taori K, Kim H, Hong J, Luesch H (2008a) Total synthesis and molecular target of largazole, a histone deacetylase inhibitor. J Am Chem Soc 130:8455–8459PubMedCrossRefGoogle Scholar
  106. Ying Y, Liu Y, Byeon SR, Kim H, Luesch H, Hong J (2008b) Synthesis and activity of largazole analogues with linker and macrocycle modification. Org Lett 10:4021–4024PubMedCrossRefGoogle Scholar
  107. Zou B, Wei J, Cai G, Ma D (2003) Synthesis of an oxazoline analogue of apratoxin A. Org Lett 5:3503–3506PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Natural Sciences and Science Education, National Institute of EducationNanyang Technological UniversitySingaporeSingapore

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