Bioactive agents from natural sources: trends in discovery and application.

About 30% of the worldwide sales of drugs are based on natural products. Though recombinant proteins and peptides account for increasing sales rates, the superiority of low-molecular mass compounds in human diseases therapy remains undisputed mainly due to more favorable compliance and bioavailability properties. In the past, new therapeutic approaches often derived from natural products. Numerous examples from medicine impressively demonstrate the innovative potential of natural compounds and their impact on progress in drug discovery and development. However, natural products are currently undergoing a phase of reduced attention in drug discovery because of the enormous effort which is necessary to isolate the active principles and to elucidate their structures. To meet the demand of several hundred thousands of test samples that have to be submitted to high-throughput screening (HTS) new strategies in natural product chemistry are necessary in order to compete successfully with combinatorial chemistry. Today, pharmaceutical companies have to spend approximately US $350 million to develop a new drug. Currently, approaches to improve and accelerate the joint drug discovery and development process are expected to arise mainly from innovation in drug target elucidation and lead finding. Breakthroughs in molecular biology, cell biology, and genetic engineering in the 1980 s gave access to understanding diseases on the molecular or on the gene level. Subsequently, constructing novel target directed screening assay systems of promising therapeutic significance, automation, and miniaturization resulted in HTS approaches changing the industrial drug discovery process drastically. Furthermore, elucidation of the human genome will provide access to a dramatically increased number of new potential drug targets that have to be evaluated for drug discovery. HTS enables the testing of an increasing number of samples. Therefore, new concepts to generate large compound collections with improved structural diversity are desirable.

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