The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an "inventory" of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered.

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C9NP00004F

Innovative omics-based approaches for prioritisation and targeted isolation of natural products – new strategies for drug discovery

CellMinerCDB for Integrative Cross-Database Genomics and Pharmacogenomics Analyses of Cancer Cell Lines.

All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high-quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity-, biology-, lead-, or fragment-oriented syntheses; and DNA-encoded libraries) are critically surveyed.

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry.

Societal Impact Statement Plants and fungi have provided, or inspired, key pharmaceuticals for global health challenges, including cancer, heart disease, dementia, and malaria, and are valued as traditional medicines worldwide. Global demand for medicinal plants and fungi has threatened certain species, contributing to biodiversity loss and depletion of natural resources that are important for the health of humanity. We consider the evolving role of plants and fungi in global healthcare as new challenges to human health and to biodiversity arise. We present current and emerging scientific approaches, to uncover and preserve nature‐based health solutions for the future, through harmonization with biodiversity conservation strategies. Summary Non‐communicable diseases, including cardiovascular disease, cancer, and diabetes, are the main causes of deaths globally, and communicable diseases such as malaria and tuberculosis affect billions of people. Plants and fungi have provided key pharmaceuticals in our armory against these global health challenges, while in some regions of the world, they continue to have a central role in healthcare systems as traditional medicines. Consequently, global demand for plants and fungi in healthcare has threatened certain medicinal species, and is a driving factor in biodiversity loss. Yet the future of therapeutics from nature is evolving. Scientific advances are enabling the untapped potential of the world's plants and fungi to be explored for their medicinal value, and to reveal other roles they may have for improving health and well‐being; this demonstrates the value of natural capital as an incentive for biodiversity conservation. Emerging technologies also offer new hope for safeguarding essential medicines for the future, by revealing more sustainable solutions for sourcing key natural products. This review discusses recent developments and future approaches for the discovery of natural products as medicines, for health and well‐being, and strategies to harmonize the therapeutic use of biodiversity with its proactive conservation through nature‐based solutions.

https://nph.onlinelibrary.wiley.com/doi/pdf/10.1002/ppp3.10138

Molecules from nature: Reconciling biodiversity conservation and global healthcare imperatives for sustainable use of medicinal plants and fungi

The US National Cancer Institute’s (NCI) Natural Product Repository is one of the world’s largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural produ...

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening

The NCI library of traditional Chinese medicinal plant extracts - Preliminary assessment of the NCI-60 activity and chemical profiling of selected species.

JA Whitt

Papers

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening

The NCI library of traditional Chinese medicinal plant extracts - Preliminary assessment of the NCI-60 activity and chemical profiling of selected species.