Abstract
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.
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References
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 96:1532–1539
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 13:4138–4152
Aráoz R, Molgó J, Tandeau de Marsac N (2010) Neurotoxic cyanobacterial toxins. Toxicon (in press)
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 59:462–469
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 34:443–456
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 4:289–292
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 50:1266–1279
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 130:11219–11222
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 11:1301–1304
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 131:2900–2905
Chen J, Forsyth CJ (2003a) Total synthesis of apratoxin A. J Am Chem Soc 125:8734–8735
Chen J, Forsyth CJ (2003b) Synthesis of the apratoxin 2,4-disubstituted thiazoline via an intramolecular Aza-Wittig reaction. Org Lett 8:1281–1283
Chen J, Forsyth CJ (2004) Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A. Proc Natl Acad Sci USA 101:12067–12072
Chen F, Gao A-H, Li J, Nan F-J (2009) Synthesis and biological evaluation of C7-demethyl largazole analogues. ChemMedChem 4:1269–1272
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 11:7825–7833
Dai L, Zhang H, Tan W, Xu Z, Ye T (2008) Total synthesis of largazole. Synlett 15:2379–2383
Doi T, Numajiri Y, Munakata A, Takahashi T (2006) Total synthesis of apratoxin A. Org Lett 8:531–534
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 11:3806–3813
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 11:7807–7816
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 45:1458–1466
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 45:115–121
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 59:1243–1245
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 75–184
Gerwick WH, Coates RC, Engene N, Gerwick L, Grindberg RV, Jones AC, Sorrels CM (2008) Giant marine cyanobacteria produce exciting potential pharmaceuticals. Microbe 3:277–284
Ghosh AK, Kulkarni S (2008) Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase. Org Lett 10:3907–3909
Gilles A, Martinez J, Cavelier F (2009) Supported synthesis of oxoapratoxin A. J Org Chem 74:4298–4304
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 17:1313–1319
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 71:1099–1103
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 59:177–189
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 61:11723–11729
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 69:572–575
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 61:1075–1077
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 65:487–491
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 62:173–180
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 13:216–123
Jordan MA, Wilson L (1998) Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 10:123–130
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 70:397–401
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 71:22–27
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 72:14–17
Liu Y, Law BK, Luesch H (2009) Apratoxin A reversibly inhibits the secretory pathway by preventing cotranslational translocation. Mol Pharmacol 76:91–104
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 63:611–615
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 64:907–910
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 123:5418–5423
Luesch H, Harrigan GG, Goetz G, Horgen FD (2002a) The cyanobacterial origin of potent anticancer agents originally isolated from sea hares. Curr Med Chem 9:1791–1806
Luesch H, Yoshida WY, Moore RE, Paul VJ (2002b) New apratoxins of marine cyanobacterial origin from Guam and Palau. Bioorg Med Chem 10:1973–1978
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 65:16–20
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 2:158–167
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 12:7615–7626
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 70:984–988
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 65:866–871
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 70:124–127
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 71:1113–1116
Matthew S, Ross C, Paul VJ, Luesch H (2008b) Pompenopeptins A and B, new cyclic peptides from the marine cyanobacterium Lyngbya confervoides. Tetrahedron 64:4081–4089
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 75:528–533
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 130:6324–6325
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 12:5207–5215
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 104:512–521
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 67:1332–1340
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 10:3595–3598
Nogle LM, Gerwick WH (2002) Somocystinamide A, a novel cytotoxic disulfide dimer from a Fijian marine cyanobacterial mixed assemblage. Org Lett 4:1095–1098
Numajiri Y, Takahashi T, Doi T (2009) Total synthesis of (−)-apratoxin A, 34-epimer, and its oxazoline analogue. Chem Asian J 4:111–125
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 328:319–324
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 107:2881–2887
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 16:893–906
Plaza A, Bewley CA (2006) Largamides A–H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp. J Org Chem 71:6898–6907
Radau G (2000) Serine protease inhibiting cyanopeptides. Pharmazie 55:555–560
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 55:181–185
Risinger AL, Giles FJ, Mooberry SL (2009) Microtubule dynamics as a target in oncology. Cancer Treatment Rev 35:255–261
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 15:671–679
Seiser T, Kamena F, Cramer N (2008) Synthesis and biological activity of largazole and derivatives. Angew Chem Int Ed 47:6483–6485
Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:1–10
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 185:629–639
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 47:3387–3390
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 431–452
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 72:1011–1016
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 11:4704–4707
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 37:6771–6774
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 60:8509–8527
Suenaga K, Kajiwara S, Kuribayashi S, Handa T, Kigoshi H (2008) Synthesis and cytotoxicity of aurilide analogs. Bioorg Med Chem Lett 18:3902–3905
Suyama TL, Gerwick WH (2008) Stereospecific total synthesis of somocystinamide A. Org Lett 10:4449–4452
Takada Y, Mori E, Umehara M, Nakao Y, Kimura J (2007) Reinvestigation of the stereochemistry of kulokekahilide-2. Tet Lett 48:7653–7656
Takada Y, Umehara M, Nakao Y, Kimura J (2008) Revised absolute stereochemistry of natural kulokekahilide-2. Tet Lett 49:1163–1165
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 5:414–428
Takahashi T, Takagi M, Shin-ya K, Doi T (2008) Total synthesis of largazole and its biological evaluation. Synlett 16:2483–2486
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 60:285–293
Tan LT (2007) Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 68:954–979
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)
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 70:1593–1600
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 130:1806–1807
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 71:1625–1629
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 10:1634–1639
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 11:5062–5065
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)
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 72:29–32
Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discovery 5:785–799
Umehara M, Takada Y, Nakao Y, Kimura J (2009) Intramolecular ester exchange of potent cytotoxic kulokekahilide-2. Tet Lett 50:840–843
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 18:905–911
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 21:297–304
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 66:1545–1549
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 281:13548–13558
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 45:1901–1917
Wipf P, Reeves JT, Day BW (2004) Chemistry and biology of curacin A. Curr Pharm Design 10:1417–1437
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 105:2313–2318
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 100:316–321
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 130:8455–8459
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 10:4021–4024
Zou B, Wei J, Cai G, Ma D (2003) Synthesis of an oxazoline analogue of apratoxin A. Org Lett 5:3503–3506
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The author would like to thank the NIE AcRF grant (RI 8/05 TLT) for financial support as well as two anonymous reviewers for their useful comments on the manuscript.
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Tan, L.T. Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery. J Appl Phycol 22, 659–676 (2010). https://doi.org/10.1007/s10811-010-9506-x
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DOI: https://doi.org/10.1007/s10811-010-9506-x