Atanas G. Atanasov et al
Re- Published under the arrangement between Sudhir Ahluwalia and Atanas G Atanasov.
Published online 2015 Aug 15. doi: 10.1016/j.biotechadv.2015.08.001
Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, the pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery sources. They are comparably easy to produce and resupply and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time, there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite its known challenges. This survey provides a brief outline of historical development and a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis.
While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will also be among the most important sources of new drugs in the future.