Natural Product Hybrids as New Leads for Drug Discovery

• Published in: Angewandte Chemie International Edition Vol. 42; no. 34; pp. 3996 - 4028
• Main Authors: Tietze, Lutz F., Bell, Hubertus P., Chandrasekhar, Srivari
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 05.09.2003; WILEY‐VCH Verlag
• Subjects: Animals; biological activity; Biological Factors - chemistry; Biological Factors - pharmacology; combinatorial chemistry; Drug Design; Drug Evaluation, Preclinical - methods; Humans; hybrids; Molecular Structure; natural products; Pharmaceutical Preparations - chemical synthesis; Pharmaceutical Preparations - chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200200553

Natural products play an important role in the development of drugs, especially for the treatment of infections and cancer, as well as immunosuppressive compounds. However, the number of natural products is limited, whereas millions of hybrids as combinations of parts of different natural products can be prepared. This new approach seems to be very promising in the development of leads for both medicinal and agrochemical applications, as the biological activity of several new hybrids exceeds that of the parent compounds. The advantage of this concept over a combinatorial chemistry approach is the high diversity and the inherent biological activity of the hybrids. Unlimited options: The synthesis of natural product hybrids by combining structurally different, naturally occurring compounds that exhibit high biological activities appears to be a promising approach to increase the number and diversity of substances for pharmacological testing. An example is the hybrid of estrone and (−)‐talaromycin (see picture).