Bio-inspiration in the discovery of active natural products: an example with the search of antifungal agents inspired from long-lasting woods

Plant natural products have been perfected through evolution with respect to their specific biological roles (defense, elicitor, and so on) and are, therefore, an excellent starting point in the search for new biologically active chemicals. Hence, despite the progressive abandonment of the exploration of naturally sourced bioactive substances by the pharmaceutical industry, more than half of the drugs approved in the United States between 2005 and 2007 are natural products or natural product-derived drugs, five of which constituted the first members of new drug classes [1]. Clearly, chemical research into natural substances still has an important role to play in improving quality of life, and can play an important role by inventing innovative strategies to discover new bioactive compounds [1,2].

In the present work, we demonstrated that a bio-inspired approach for the identification of novel bioactive natural products represents a promising biotechnological tool for the development of new drugs. We have studied how natural defenses within decay-resistant wood can generate a large number of positive hits in the search for antimycotic agents. In addition, it was found from bioguided fractionation that ethyl acetate extracts of Sextonia rubra wood contain a relatively large proportion of antifungal metabolites rubrenolide (1) and rubrynolide (2), 1 being slightly more active than 2. The therapeutic potential of the above compounds will be discussed through the evaluation of their antifungal activities against 16 pathogenic fungi strains and their cytotoxicities towards KB cells.

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Acknowledgements: The authors gratefully acknowledge the Programme Amazonie du CNRS (France), CAPES, CNPq and FAPDF (Brazil) for financial support.

References: 1. Li, J. W.-H. et al. (2009) Science 325: 161–165.

2. Dobson, C. M. (2004) Nature 432: 824–828.