Natural Product Synthesis and Drug Discovery: Shortcomings and Successes

https://doi.org/10.26538/tjnpr/v1i3.1

Abstract

Natural products have evolved over the years and several of them have been found to interact with biological macromolecules in intact
organisms. Their structural complexity often makes it difficult to produce natural drug molecules via chemical synthesis. This limitation can hinder their further development as drugs. Modification of a natural product’s structure by chemical synthesis to address issues of unwanted side effects can also be very difficult. As an alternative to chemical synthesis, the natural products are isolated in commercial quantities from their sources. This however, poses other challenges such as the need to obtain enough raw material in an environmentally sustainable fashion to ensure an adequate supply of the drug. There is also variability in how some substances produce often trace amounts of potential drugs. In the pharmaceutical industry, such drawbacks have led to the deprioritization of natural products as drug leads, or even in the total elimination of natural product-based drug discovery efforts, in favor of studying and developing smaller, lower molecular weight molecules, substances that are more easily synthesized and modified. The shift away from natural products as leads is perhaps unfortunate, given their impressive track record as effective drugs, particularly in the fields of cancer therapy and the treatment of infectious diseases.