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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | López, Silvia N. Sierra, Manuel Gonzalez Ramallo, I. Ayelen Zacchino, Susana A. Furlan, Ricardo L. E. |
| Description | Author Affiliation: López SN ( Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 531, S2002LRK Rosario, Argentina.); |
| Abstract | The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Biological Products Chemical Synthesis Chemical Engineering Drug Design Antifungal Agents Chemistry Pharmacology Candida Albicans Drug Effects Chromatography, High Pressure Liquid Hydrazines Indicators And Reagents Magnetic Resonance Spectroscopy Microbial Sensitivity Tests Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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