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The Past, Present and Future of Plant Natural Product Chemistry

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Natural products (NPs) (secondary metabolites) from terrestrial and marine organisms have evolved over thousands of years to combat environmental factors such as weather and predation producing new chemical entities (NCE's). They have been the stronghold of disease therapy for most of human history and are a ...

Natural products (NPs) (secondary metabolites) from terrestrial and marine organisms have evolved over thousands of years to combat environmental factors such as weather and predation producing new chemical entities (NCE's). They have been the stronghold of disease therapy for most of human history and are a major source of modern pharmaceuticals, predominantly derived from plant origin. Following the discovery of the penicillins, drug discovery from microbial sources occurred and with the advancement of diving techniques in the 1970s subsequently opened the seas as a potential source of NPs. Chemical synthesis shifted the focus of drug discovery efforts from nature to the laboratory bench in the late 1980s. Out of the 1135 new drugs approved from 1981-2010, 50% are of NP origin (derivatives and/or analogues). One famous example includes the breast cancer drug paclitaxel (Taxol®), isolated from the bark of Pacific Yew tree. Of course, a NP discovery program endeavors to search for novel bioactive NPs, nevertheless, the isolation of known, abundant NPs with no chemical or pharmacological interest is inevitable. The process of identifying known NPs responsible for the activity of an extract prior to bioassay-guided isolation is referred to as dereplication and it is estimated that it takes $US 50,000 and 3 months of work to isolate and identify an active NP. Given this major bottleneck many pharmaceutical companies decommissioned their programs or ceased investing in high-throughput screening (HTS) programs in the early 2000s and it appeared that NP discovery was at the end of its era.

In our opinion, NP discovery is still active and the isolation of novel bioactive natural products has strengthened due to the improvement in sensitive separation methods, mass spectrometry and nuclear magnetic resonance spectroscopy. Furthermore, recent advancements in comprehensive analytical platforms and emerging fields such as, metabolomics are now being integrated with NP chemistry to dereplicate and profile NP extracts efficiently. Isolating the elusive ‘needle-in-the-haystack’ or ‘magic-bullet’ appears to be an old paradigm and research seems to be shifting towards multi-target studies on NP extracts (botanicals and herbal formulations). For example, China, India and Germany still teach phytotherapy in medical schools and practice herbal medicine suggesting that the use of botanicals could be a solution for industrialized countries facing dramatic health costs increases with single NP derived medicine. Translational medicine, evidence based phytotherapy and new progresses in NP extract studies will provide new sources of innovation in the future.

This research topic is aimed at providing insight into the history of NP chemistry with the focus on plant bioactives, its current state and how this classical science will progress in the future. Topics sort to be discussed include: historical and current uses of NPs and perspectives; traditional medicines/formulations and synergism; drug interactions with botanicals/herbs; reverse-pharmacognosy; high through-put screening versus evidence based; access and benefit sharing and application of current advanced analytical systems such as metabolomics with NP chemistry. Both, reviews, original articles as well as expert opinions are welcome.


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