THE CONTINUING VALUE OF NATURAL PRODUCTS FOR DRUG DISCOVERY

Abstract

Natural products are the most consistently successful source of drug leads, both historically and currently. Despite this, the use of natural products in industrial drug discovery has fallen out of
favour. Natural products are likely to continue to be sources of new commercially viable drug leads because the chemical novelty associated with natural products is higher than that of any other source: this is particularly important when searching for lead molecules against newly discovered targets for
which there are no known small molecule leads. Despite the commonly held assumptions, natural products can be a more economical source of chemical diversity compared with synthesis of equivalent numbers of diverse chemicals. Additionally, natural products that are found to be biologically active in assays are generally small molecules with drug-like properties. That is, they are capable of being absorbed and metabolised by the body. Hence, development costs to produce orally active medicines are likely to be much lower than with biotechnological products or with most compounds produced to
date from combinatorial chemistry. Since less than 10% of the world’s biodiversity is reckoned to have been tested for biological activity, many more useful lead compounds are waiting to be discovered from natural products. The challenge is how to access this natural chemical diversity. Several different
strategies are emerging, as will be described in this review.