Natural products as a screening resource.

Natural products have been the most productive source of leads for new drugs, but they are currently out of fashion with the pharmaceutical industry. New approaches to sourcing novel compounds from untapped areas of biodiversity coupled with the technical advances in analytical techniques (such as microcoil NMR and linked LC-MS-NMR) have removed many of the difficulties in using natural products in screening campaigns. As the 'chemical space' occupied by natural products is both more varied and more drug-like than that of combinatorial chemical collections, synthetic and biosynthetic methods are being developed to produce screening libraries of natural product-like compounds. A renaissance of drug discovery inspired by natural products can be predicted.

[1]  U. Abel,et al.  Modern methods to produce natural-product libraries. , 2002, Current opinion in chemical biology.

[2]  Thomas Henkel,et al.  Statistical Investigation into the Structural Complementarity of Natural Products and Synthetic Compounds. , 1999, Angewandte Chemie.

[3]  J. F. Nunn,et al.  Interaction of nitrous oxide and vitamin B12 , 1984 .

[4]  Jean-Luc Wolfender,et al.  Phytochemistry in the microgram domain—a LC–NMR perspective , 2005, Magnetic resonance in chemistry : MRC.

[5]  Y. Feng,et al.  Use of biomimetic diversity-oriented synthesis to discover galanthamine-like molecules with biological properties beyond those of the natural product. , 2001, Journal of the American Chemical Society.

[6]  Herbert Waldmann,et al.  Compound library development guided by protein structure similarity clustering and natural product structure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Schuffenhauer,et al.  Charting biologically relevant chemical space: a structural classification of natural products (SCONP). , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. M. Boldi,et al.  Libraries from natural product-like scaffolds. , 2004, Current opinion in chemical biology.

[9]  Christopher T. Walsh,et al.  Lessons from natural molecules , 2004, Nature.

[10]  K U. Bindseil,et al.  Pure compound libraries; a new perspective for natural product based drug discovery. , 2001, Drug discovery today.

[11]  M. O'Neil-Johnson,et al.  High-throughput method for the production and analysis of large natural product libraries for drug discovery. , 2002, Analytical chemistry.

[12]  K. S. Lam,et al.  Discovery of novel metabolites from marine actinomycetes. , 2006, Current opinion in microbiology.

[13]  M. O'Neil-Johnson,et al.  Application of capillary-scale NMR for the structure determination of phytochemicals. , 2005, Phytochemical analysis : PCA.

[14]  W. Sneader.  Drug prototypes and their exploitation , 1996 .

[15]  J L Wolfender,et al.  The potential of LC-NMR in phytochemical analysis. , 2001, Phytochemical analysis : PCA.

[16]  Marcel Jaspars,et al.  Biomedical research tools from the seabed. , 2007, Current opinion in drug discovery & development.

[17]  J. Marchesi,et al.  Metagenomic approaches to exploit the biotechnological potential of the microbial consortia of marine sponges , 2007, Applied Microbiology and Biotechnology.

[18]  Jean-Luc Wolfender,et al.  Identification of natural products using HPLC-SPE combined with CapNMR. , 2007, Analytical chemistry.

[19]  George G Harrigan,et al.  Chemical and biological integrity in natural products screening. , 2005, Combinatorial chemistry & high throughput screening.

[20]  Klaus Albert,et al.  LC–NMR coupling technology: recent advancements and applications in natural products analysis , 2005, Magnetic resonance in chemistry : MRC.

[21]  Guido F Pauli,et al.  Quantitative 1H NMR: development and potential of a method for natural products analysis. , 2005, Journal of natural products.

[22]  G. Bringmann,et al.  Full absolute stereostructures of natural products directly from crude extracts: The HPLC-MS/ MS-NMR-CD 'triad'. , 2003, Progress in molecular and subcellular biology.

[23]  Lars Bohlin,et al.  Unconventional natural sources for future drug discovery. , 2004, Drug discovery today.

[24]  Jørn Smedsgaard,et al.  Phenotypic taxonomy and metabolite profiling in microbial drug discovery. , 2005, Natural product reports.

[25]  A. Harvey,et al.  Strategies for discovering drugs from previously unexplored natural products. , 2000, Drug discovery today.

[26]  David J Newman,et al.  Natural products as sources of new drugs over the period 1981-2002. , 2003, Journal of natural products.

[27]  Lars Bohlin,et al.  Functional versus chemical diversity: is biodiversity important for drug discovery? , 2002, Trends in pharmacological sciences.

[28]  Erich von Roedern,et al.  High-throughput purification of single compounds and libraries. , 2005, Journal of combinatorial chemistry.

[29]  Burkhard Haefner,et al.  Drugs from the deep: marine natural products as drug candidates. , 2003, Drug discovery today.

[30]  F. Schroeder,et al.  Extending the scope of NMR spectroscopy with microcoil probes. , 2006, Angewandte Chemie.

[31]  Mohamed A. Marahiel,et al.  Chemoenzymatic and Template-Directed Synthesis of Bioactive Macrocyclic Peptides , 2006, Microbiology and Molecular Biology Reviews.

[32]  Lu Zeng,et al.  High-throughput analysis of natural product compound libraries by parallel LC-MS evaporative light scattering detection. , 2002, Analytical chemistry.

[33]  Marcy J. Balunas,et al.  Drug discovery from natural sources , 2006, The AAPS Journal.

[34]  M. Butler.  Natural products to drugs: natural product-derived compounds in clinical trials. , 2005, Natural product reports.

[35]  Oliver Schwarz,et al.  Natural products in combinatorial chemistry: an andrographolide-based library. , 2006, Journal of combinatorial chemistry.

[36]  Jacques Ravel,et al.  Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians , 2006, Nature chemical biology.

[37]  Phillip C. Wright,et al.  Genetic analysis of polyketide synthase and peptide synthetase genes in cyanobacteria as a mining tool for secondary metabolites , 2007, Journal of Industrial Microbiology & Biotechnology.

[38]  Lars Ole Haustedt,et al.  Rational approaches to natural-product-based drug design. , 2006, Current opinion in drug discovery & development.

[39]  K. S. Lam,et al.  New aspects of natural products in drug discovery. , 2007, Trends in microbiology.

[40]  R. Furlan,et al.  Chemically engineered extracts as an alternative source of bioactive natural product-like compounds , 2007, Proceedings of the National Academy of Sciences.

[41]  K. Gustafson,et al.  Marine pharmacology in 2003-2004: anti-tumour and cytotoxic compounds. , 2006, European journal of cancer.

[42]  Cristina Draghici,et al.  Molecular formula analysis by an MS/MS/MS technique to expedite dereplication of natural products. , 2007, Analytical chemistry.

[43]  Sylvie Lautru,et al.  Discovery of a new peptide natural product by Streptomyces coelicolor genome mining , 2005, Nature chemical biology.

[44]  Agnieszka Ulaczyk-Lesanko,et al.  Wanted: new multicomponent reactions for generating libraries of polycyclic natural products. , 2005, Current opinion in chemical biology.

[45]  Miklos Feher,et al.  Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry , 2003, J. Chem. Inf. Comput. Sci..

[46]  Heinz G Floss,et al.  Combinatorial biosynthesis--potential and problems. , 2006, Journal of biotechnology.

[47]  Oliver Zerbe,et al.  Strategies and Tools for Structure Determination of Natural Products Using Modern Methods of NMR Spectroscopy , 2005, Chemistry & biodiversity.

[48]  Sorel Muresan,et al.  ChemGPS-NP: tuned for navigation in biologically relevant chemical space. , 2006, Journal of natural products.

[49]  D. Faulkner,et al.  Marine natural products. , 1996, Natural product reports.