Optimization Of Natural Product Leads

Nature has preserved the ability of a given organism to make these fascinating secondary metabolites, although their inherent biological roles remain obscure. As scientists seek to co-opt these metabolites as medicinal agents, attempts are typically made to enhance their pharmaceutical effectiveness. Such enhancements may be to improve the spectrum of activity against a range of targets, as in the case of antibiotics where broad-spectrum activity in inhibiting the growth of both grampositive and gram-negative bacteria is important. In other cases it may be crucial to enhance the specificity to a narrower range of targets, such as the ability to selectively inhibit a particular kinase reaction in a signaling cascade. Furthermore, it may be necessary to improve the drug-like properties of a natural product lead. Here improvements in solubility, chemical stability in biological matrices or metabolic stability may be crucial. These and a host of other reasons drive the process to make structural modifications of the core natural product, which may be effected by chemical or biosynthetic means.

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