Phytochemistry Reviews

, Volume 8, Issue 2, pp 313–331 | Cite as

Nature: a vital source of leads for anticancer drug development



Over 60% of the current anticancer drugs have their origin in one way or another from natural sources. Nature continues to be the most prolific source of biologically active and diverse chemotypes, and it is becoming increasingly evident that associated microbes may often be the source of biologically active compounds originally isolated from host macro-organisms. While relatively few of the actual isolated compounds advance to become clinically effective drugs in their own right, these unique molecules may serve as models for the preparation of more efficacious analogs using chemical methodology such as total or combinatorial (parallel) synthesis, or manipulation of biosynthetic pathways. In addition, conjugation of toxic natural molecules to monoclonal antibodies or polymeric carriers specifically targeted to epitopes on tumors of interest can lead to the development of efficacious targeted therapies. The essential role played by natural products in the discovery and development of effective anticancer agents, and the importance of multidisciplinary collaboration in the generation and optimization of novel molecular leads from natural product sources is reviewed.


Plants Marine organisms Microbes Symbionts Multidisciplinary collaboration 


  1. Abe F, Horikoshi K (2001) The biotechnological potential of piezophiles. Trends Biotechnol 19:102–108PubMedGoogle Scholar
  2. Agoulnik S, Kuznetsov G, Tendyke K et al (2005) Sensitivity to halichondrin analog E7389 and hemiasterlin analog E7974 correlates with beta III tubulin isotype expression in human breast cancer cell lines. In: 41st Annual Meeting of American Society of Clinical Oncology (ASCO), Abstract 2012Google Scholar
  3. Alhamadsheh MM, Hudson RA, Tillekeratne LMV (2006) Design, total synthesis, and evaluation of novel open-chain epothilone analogues. Org Lett 8:685–688PubMedGoogle Scholar
  4. Altmann K-H (2005) Recent developments in the chemical biology of epothilones. Curr Pharm Des 11:1595–1613PubMedGoogle Scholar
  5. Amna T, Puri SC, Verma V et al (2006) Bioreactor studies on the endophytic fungus Entrophospora infrequens for the production of an anticancer alkaloid camptothecin. Can J Microbiol 52:189–196PubMedGoogle Scholar
  6. Andersen RJ, Roberge M (2005) HTI-286, a synthetic analog of the antimitotic natural product hemiasterlin. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 267–280Google Scholar
  7. Arcamone F (2005) Anthracyclines. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 299–320Google Scholar
  8. Bai R, Pettit GR, Hamel E (1990) Dolastatin 10, a powerful cytostatic peptide derived from a marine animal: inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. Biochem Pharmacol 39:1941–1949PubMedGoogle Scholar
  9. Banskota AH, McAlpine JB, Sørensen D et al (2006) Genomic analyses lead to novel secondary metabolites. Part 3. ECO-0501, a novel antibacterial of a new class. J Antibiot 59:533–542PubMedGoogle Scholar
  10. Bode HB, Muller R (2005) The impact of bacterial genomics on natural product research. Angew Chem Int Ed 44:6828–6846Google Scholar
  11. Bok JW, Hoffmeister D, Maggio-Hall LA et al (2006) Genomic mining for Aspergillus natural products. Chem Biol 13:31–37PubMedGoogle Scholar
  12. Borman S (2003) The many faces of combinatorial chemistry. Chem Eng News 81(43):45–56Google Scholar
  13. Borman S (2004) Rescuing combichem. Chem Eng News 82(40):32–40Google Scholar
  14. Byrd JC, Peterson BL, Gabrilove J, Odenike et al (2005) Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: results from cancer and leukemia group B study 19805. Clin Cancer Res 11:4176PubMedGoogle Scholar
  15. Cachoux F, Isarno T, Wartmann M et al (2005) Scaffolds for microtubule inhibition through extensive modification of the epothilone template. Angew Chem Int Ed 44:7469–7473Google Scholar
  16. Cassady JM, Chan KK, Floss HG et al (2004) Recent developments in the maytansinoid antitumor agents. Chem Pharm Bull (Tokyo) 52:1–26Google Scholar
  17. Cavicchioli R, Siddiqui KS, Andrews D et al (2002) Low-temperature extremophiles and their applications. Curr Opin Biotechnol 13:253–261PubMedGoogle Scholar
  18. Chang YT, Gray NS, Rosania GR et al (1999) Synthesis and application of functionally diverse 2, 6, 9-trisubstituted purine libraries as CDK inhibitors. Chem Biol 6:361–375PubMedGoogle Scholar
  19. Clardy J, Walsh CT (2004) Lessons from natural molecules. Nature 432:829–837PubMedGoogle Scholar
  20. Clardy J, Fischbach MA, Walsh CT (2006) New antibiotics from bacterial natural products. Nature Biotechnol 24:1541–1550Google Scholar
  21. Class S (2002) Pharma overview. Chem Eng News 80(48):39–49Google Scholar
  22. Cortes JE, Pazdur R (1995) Docetaxel. J Clin Oncol 13:2643–2655PubMedGoogle Scholar
  23. Cragg GM, Newman DJ (2004) A tale of two tumor targets: topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy. J Nat Prod 67:232–244PubMedGoogle Scholar
  24. Cunningham C, Appleman LJ, Kirvan-Visovatti M et al (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 11:7825–7833PubMedGoogle Scholar
  25. de Jonge M, Verweiji J (2005) The epothilone dilemma. J Clin Oncol 23:9048–9050PubMedGoogle Scholar
  26. Denmeade SR, Jakobsen CM, Janssen S et al (2003) Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. J Nat Cancer Inst 95:990–1000PubMedCrossRefGoogle Scholar
  27. Duncan R (1997) Drug targeting: where are we now and where are we going? J Drug Target 5:1–4PubMedCrossRefGoogle Scholar
  28. Ebbinghaus S, Rubin E, Hersh E et al (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 11:7807–7816PubMedGoogle Scholar
  29. Engert A, Sausville EA, Vitetta E (1998) The emerging role of ricin A-chain immunotoxins in leukemia and lymphoma. Curr Top Microbiol Immunol 234:13–33PubMedGoogle Scholar
  30. Evert S (2008) Peptide-producing powerhouses. Chem Eng News 86(43):48–50Google Scholar
  31. Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J Nat Prod 69:1121–1124PubMedGoogle Scholar
  32. Ezra D, Castillo UF, Strobel GA et al (2004) Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU 2110) endophytic on monstera sp. Microbiology 150:785–793PubMedGoogle Scholar
  33. Feling RH, Buchanan GO, Mincer TJ et al (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angew Chem Int Ed 42:355–357Google Scholar
  34. Fieseler L, Hentschel U, Grozdanov L et al (2007) Widespread occurrence and genomic context of unusually small polyketide synthase genes in microbial consortia associated with marine sponges. J Appl Environ Microbiol 73:2144–2155Google Scholar
  35. Flahive E, Srirangam J (2005) The dolastatins: novel antitumor agents from Dolabella auricularia. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 191–214Google Scholar
  36. Gomes J, Steiner W (2004) Extremophiles and extremozymes. Food Technol Biotechnol 42:223–235Google Scholar
  37. Gontang EA, Fenical W, Jensen PR (2007) Phylogenetic diversity of gram-positive bacteria cultured from marine sediments. Appl Environ Microbiol 73:3272–3282PubMedGoogle Scholar
  38. Gueritte F, Fahy J (2005) The vinca alkaloids. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 123–136Google Scholar
  39. Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod 69:509–526PubMedGoogle Scholar
  40. Hale KJ, Hummersone MG, Manaviazar S et al (2002) The chemistry and biology of the bryostatin antitumour macrolides. Nat Prod Rep 19:413–453PubMedGoogle Scholar
  41. Hecht SM (2005) Bleomycin group antitumor agents. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 357–382Google Scholar
  42. Henríquez R, Faircloth G, Cuevas C (2005) Ecteinascidin 743 (ET-743, Yondelis), aplidin, and kahalalide F. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 215–240Google Scholar
  43. Herbst RS, Hammond LA, Carbone DP et al (2003) A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res 9:4108–4115PubMedGoogle Scholar
  44. Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24:393–416PubMedGoogle Scholar
  45. Höfle G, Reichenbach H (2005) Epothilone, a myxobacterial metabolite with promising antitumor activity. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 413–450Google Scholar
  46. Hoyoux A, Blaise V, Collins T et al (2004) Extreme catalysts from low-temperature environments. Biosci Bioeng 98:317–330Google Scholar
  47. Itokawa H, Wang X, Lee K-H (2005) Homoharringtonine and related compounds. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 47–70Google Scholar
  48. Janssen S, Rosen DM, Ricklis RM et al (2006) Pharmacokinetics, biodistribution and antitumor efficacy of a human glandular kallikrein 2 (hK2)-activated thapsigargin prodrug. Prostate 66:358–368PubMedGoogle Scholar
  49. Johnson DB, Hallberg KB (2003) The microbiology of acidic mine waters. Res Microbiol 154:466–473PubMedGoogle Scholar
  50. Khosla C (2000) Natural product biosynthesis: a new interface between enzymology and medicine. J Org Chem 65:8127–8133PubMedGoogle Scholar
  51. Kingston DGI (2005) Taxol and its analogs. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 89–122Google Scholar
  52. Kwon HC, Kauffman CA, Jensen PR et al (2006) Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus “marinispora”. J Am Chem Soc 128:1622–1632PubMedGoogle Scholar
  53. Lam KS (2007) New aspects of natural products in drug discovery. Trends Microbiol 15:279–289PubMedGoogle Scholar
  54. Lee K-H, Xiao Z (2005) Podophyllotoxins and analogs. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 71–88Google Scholar
  55. Li Q, Sham HL (2002) Discovery and development of antimitotic agents that inhibit tubulin polymerisation for the treatment of cancer expert. Opin Ther Pat 12:1663–1701Google Scholar
  56. McAlpine JB, Bachmann BO, Piraee M et al (2005) Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent as an example. J Nat Prod 68:493–496PubMedGoogle Scholar
  57. Meijer L, Raymond E (2003) Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc Chem Res 36:417–425PubMedGoogle Scholar
  58. Melnikova I (2005) Wet age-related macular degeneration. Nat Rev Drug Discov 4:711–712PubMedGoogle Scholar
  59. Moore KS, Wehrli S, Roder H et al (1993) Squalamine: an aminosterol antibiotic from the shark. Proc Natl Acad Sci USA 90:1354–1358PubMedGoogle Scholar
  60. Mutter R, Wills M (2000) Chemistry and clinical biology of the bryostatins. Bioorg Med Chem 8:1841–1860PubMedGoogle Scholar
  61. Newman DJ (2005) The bryostatins. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 137–150Google Scholar
  62. Newman DJ, Cragg GM (2004) Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod 67:1216–1238PubMedGoogle Scholar
  63. Newman DJ, Cragg GM (2005) The discovery of anticancer drugs from natural sources. In: Zhang L, Fleming GA, Demain AL (eds) Natural products: drug discovery. Therapeutics, and preventative medicine. Dekker, New York, pp 129–168Google Scholar
  64. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:1022–1037Google Scholar
  65. Nicolaou KC, Vourloumis D, Winssinger N et al (2000) The art and science of total synthesis at the dawn of the twenty-first century. Angew Chem Int Ed 39:44–122Google Scholar
  66. Norcross RD, Patterson I (1995) Total synthesis of bioactive marine macrolides. Chem Rev 95:2041–2114Google Scholar
  67. Oh DC, Strangman WK, Kauffman CA et al (2007) Thalassospiramides A and B, immunosuppressive peptides from the marine bacterium Thalassospira sp. Org Lett 9:1525–1528PubMedGoogle Scholar
  68. Partida-Martinez LP, Hertweck C (2005) Pathogenic fungus harbours endosymbiotic bacteria for toxin production. Nature 437:884–888PubMedGoogle Scholar
  69. Pennati M, Capmpbell AJ, Curto M et al (2005) Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther 4:1328–1337PubMedGoogle Scholar
  70. Persidis A (1998) Extremophiles. Nature Biotechnol 16:593–594Google Scholar
  71. Piel J (2004) Metabolites from symbiotic bacteria. Nat Prod Rep 21:519–538PubMedGoogle Scholar
  72. Piel J (2006) Bacterial symbionts: prospects for the sustainable production of invertebrate-derived pharmaceuticals. Curr Med Chem 13:39–50PubMedGoogle Scholar
  73. Piel J, Hofer I, Hui D (2004a) Evidence for a symbiosis island involved in horizontal acquisition of pederin biosynthetic capabilities by the bacterial symbiont of Paederus fuscipes beetles. J Bacteriol 186:1280–1286PubMedGoogle Scholar
  74. Piel J, Hui D, Wen G et al (2004b) Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei. Proc Natl Acad SciUSA 101:16222–16227Google Scholar
  75. Piel J, Butzke D, Fusetani N et al (2005) Exploring the chemistry of uncultivated bacterial symbionts: antitumor polyketides of the pederin family. J Nat Prod 68:472–479PubMedGoogle Scholar
  76. Pinney KG, Jelinek C, Edvardsen K (2005) The discovery and development of the combretastatins. In: Cragg GM, Kingston DGI, Newman DJ et al (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 23–46Google Scholar
  77. Puri SC, Verma V, Amna T et al (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719PubMedGoogle Scholar
  78. Rachid S, Gerth K, Kochems I et al (2007) Deciphering regulatory mechanisms for secondary metabolite production in the myxobacterium Sorangium cellulosum So ce56. Mol Microbiol 63:1783–1796PubMedGoogle Scholar
  79. Rademaker-Lakhai JM, Horenblas S, Meinhardt W et al (2005) Phase I clinical and pharmokinetic study of kahalalide F in patients with advanced androgen refractory prostate cancer. Clin Cancer Res 11:1854–1862PubMedGoogle Scholar
  80. Rahier NJ, Thomas CJ, Hecht SM (2005) Camptothecin and its analogs. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 5–22Google Scholar
  81. Rasila KK, Verschraegen C (2005) Tasidotin HCI. Curr Opin Investig Drugs 6:631–638PubMedGoogle Scholar
  82. Rondon MR, August PR, Bettermann AD et al (2000) Cloning the soil metagenome: a strategy for accessing the genetic and functional diversity of uncultured microorganisms. Appl Environ Microbiol 66:2541–2547PubMedGoogle Scholar
  83. Rose V, Schiller J, Wood A et al (2004) Randomized phase II trial of weekly squalamine, carboplatin, and paclitaxel as first line therapy for advanced non-small cell lung cancer. J Clin Oncol 22: 7109 (Meeting Abstracts)Google Scholar
  84. Rossi M, Ciaramella M, Cannio R et al (2003) Extremophiles 2002. J Bacteriol 185:3683–3689PubMedGoogle Scholar
  85. Salazar R, Casado E, Lopez Martin JA et al (2005) Clinical and pharmacokinetic phase I dose-finding study of kahalalide F (KF) administered as a prolonged infusion in patients with solid tumors. J Clin Oncol 23(16S): Abstract 2059Google Scholar
  86. Sausville EA, Zaharevitz D, Gussio R et al (1999) Cyclin-dependent kinases: initial approaches to exploit a novel therapeutic target. Pharmacol Ther 82:285–292PubMedGoogle Scholar
  87. Schiraldi C, De Rosa M (2002) The production of biocatalysts and biomolecules from extremophiles. Trends Biotechnol 20:515–521PubMedGoogle Scholar
  88. Shimoyama T, Hamano T, Natsume T et al (2006) Reference profiling of the genomic response induced by an antimicrotubule agent, TZT-1027 (soblidotin), in vitro. Pharmacogenom J 6:388–396Google Scholar
  89. Short PL (2007) New Zealand plays to its strengths. Chem Eng News 85(4):20–21Google Scholar
  90. Sills AK Jr, Williams JI, Tyler BM et al (1998) Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Res 58:2784–2792PubMedGoogle Scholar
  91. Sohoel H, Jensen AM, Moller JV et al (2006) Natural products as starting materials for development of second-generation SERCA inhibitors targeted towards prostate cancer cells. Bioorg Med Chem 14:2810–2815PubMedGoogle Scholar
  92. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416PubMedGoogle Scholar
  93. Stierle AE, Stierle DB, Patacinni B (2008) The berkeleyamides, amides from the acid lake fungus Penicillium rubrum. J Nat Prod 71(5):856–860PubMedGoogle Scholar
  94. Strobel GA, Daisy B, Castillo U et al (2004) Natural products from endophytic microorganisms. J Nat Prod 67:257–268PubMedGoogle Scholar
  95. Sudek S, Lopanik NB, Waggoner LE et al (2007) Identification of the putative polyketide gene cluster from the uncultivated microbial symbiont, Candidatus Endobugula sertula, of the marine bryozoan, Bugula neritina. J Nat Prod 70:67–74PubMedGoogle Scholar
  96. Tan RX, Zou WX (2001) Endophytes: a rich source of functional metabolites. Nat Prod Rep 18:448–459PubMedGoogle Scholar
  97. Tang L, Chung L, Carney JR et al (2005) Generation of new epothilones by genetic engineering of a polyketide synthase in Myxococcus xanthus. J Antibiot 58:178–184PubMedGoogle Scholar
  98. Thomas MG, Bixby KA, Shen B (2005) Combinatorial biosynthesis of anticancer natural products. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 519–552Google Scholar
  99. Udwary DW, Zeigler L, Asolkar RN et al (2007) Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc Natl Acad Sci USA 104:10376–10381PubMedGoogle Scholar
  100. Van de Weghe P, Eustache J (2005) The application of olefin metathesis to the synthesis of biologically active macrocyclic agents. Curr Top Med Chem 5:1495–1519PubMedGoogle Scholar
  101. van den Burg B (2003) Extremophiles as a source for novel enzymes. Curr Opin Microbiol 6:213–218PubMedGoogle Scholar
  102. Venter JC, Remington K, Heidelberg JF et al (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304:66–74PubMedGoogle Scholar
  103. Walsh CT (2004) Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science 303:1805–1810PubMedGoogle Scholar
  104. Walsh CT (2007) The chemical versatility of natural-product assembly lines. Acc Chem Res 41:4–10PubMedGoogle Scholar
  105. Warnecke F, Luginbühl P, Ivanova N et al (2007) Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450:560–565PubMedGoogle Scholar
  106. Wender PA, Lippa B (2000) Synthesis and biological evaluation of bryostatin analogues: the role of the A-ring. Tetrahedron Lett 41:1007–1011Google Scholar
  107. Wender PA, De Brabander J, Harran PG et al (1998a) Synthesis of the first members of a new class of biologically active bryostatin analogues. J Am Chem Soc 120:4534–4535Google Scholar
  108. Wender PA, De Brabander J, Harran PG et al (1998b) The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1. Proc Natl Acad Sci USA 95:6624–6629PubMedGoogle Scholar
  109. Wender PA, Hinkle KW, Koehler MFT et al (1999) The rational design of potential chemotherapeutic agents: synthesis of bryostatin analogues. Med Res Rev 19:388–407PubMedGoogle Scholar
  110. Wender PA, Baryza JL, Bennett CE et al (2002) The practical synthesis of a novel and highly potent analogue of bryostatin. J Am Chem Soc 124:13648–13649PubMedGoogle Scholar
  111. Wender PA, Mayweg AVW, VanDeusen CL (2003a) A concise, selective synthesis of the polyketide spacer domain of a potent bryostatin analogue. Org Lett 5:277–279PubMedGoogle Scholar
  112. Wender PA, Koehler MFT, Sendzik M (2003b) A new synthetic approach to the C ring of known as well as novel bryostatin analogues. Org Lett 5:4549–4552PubMedGoogle Scholar
  113. Wiegel J, Kevbrin VV (2004) Alkalithermophiles. Biochem Soc Trans 32:193–198PubMedGoogle Scholar
  114. Wilkinson B, Moss SJ (2005) Biosynthetic engineering of natural products for lead optimization and development. Curr Opin Drug Dis Dev 8:748–750Google Scholar
  115. Williams PG, Asolkar RN, Kondratyuk T et al (2007) Saliniketals A and B, bicyclic polyketides from the marine actinomycete Salinispora arenicola. J Nat Prod 70:83–88PubMedGoogle Scholar
  116. Yang X, Zhang L, Guo B et al (2004) Preliminary study of a vincristine-producing endophytic fungus isolated from leaves of Catharanthus roseus. Zhong Cao Yao (Chinese Tradit. Herb. Drugs) 35:79–81Google Scholar
  117. Yooseph S, Sutton G, Rusch DB et al (2007) The sorcerer II global ocean sampling expedition: expanding the universe of protein families. PLoS Biol 5(3):e16 doi: 10.1371/journal.pbio.0050016. (Published 13 March 2007)
  118. Yu T-W, Floss HG (2005) Ansamitocins (Maytansanoids). In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 321–338Google Scholar
  119. Yu MJ, Kishi Y, Littlefield BA (2005) Discovery of E7389, a fully synthetic macrocyclic ketone analog of halichondrin B. In: Cragg GM, Kingston DGI, Newman DJ (eds) Anticancer agents from natural products. Taylor and Francis, Boca Raton, pp 241–266Google Scholar
  120. Zhou G-X, Wijeratne EMK, Bigelow D et al (2004) Aspochalasins I, J, and K. J Nat Prod 67:328–332PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and DiagnosisUS National Cancer InstituteFrederickUSA

Personalised recommendations