Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery

Abstract

The therapeutic properties of plants have been recognised since time immemorial. Many pathological conditions have been treated using plant-derived medicines. These medicines are used as concoctions or concentrated plant extracts without isolation of active compounds. Modern medicine however, requires the isolation and purification of one or two active compounds. There are however a lot of global health challenges with diseases such as cancer, degenerative diseases, HIV/AIDS and diabetes, of which modern medicine is struggling to provide cures. Many times the isolation of "active compound" has made the compound ineffective. Drug discovery is a multidimensional problem requiring several parameters of both natural and synthetic compounds such as safety, pharmacokinetics and efficacy to be evaluated during drug candidate selection. The advent of latest technologies that enhance drug design hypotheses such as Artificial Intelligence, the use of 'organ-on chip' and microfluidics technologies, means that automation has become part of drug discovery. This has resulted in increased speed in drug discovery and evaluation of the safety, pharmacokinetics and efficacy of candidate compounds whilst allowing novel ways of drug design and synthesis based on natural compounds. Recent advances in analytical and computational techniques have opened new avenues to process complex natural products and to use their structures to derive new and innovative drugs. Indeed, we are in the era of computational molecular design, as applied to natural products. Predictive computational softwares have contributed to the discovery of molecular targets of natural products and their derivatives. In future the use of quantum computing, computational softwares and databases in modelling molecular interactions and predicting features and parameters needed for drug development, such as pharmacokinetic and pharmacodynamics, will result in few false positive leads in drug development. This review discusses plant-based natural product drug discovery and how innovative technologies play a role in next-generation drug discovery.

Keywords: automation; bioinformatics; computational softwares; drug design and development; global health; innovation; natural products; omics; precision medicine.

Figure 1

Two examples of successful stories of plant natural products that are being used in hospitals and clinics for disease treatment. (A) Morphine is isolated from Papaver somniferum also called opium poppy (B) Paclitaxel is isolated from Taxus brevifolia also called pacific yew. (Images credit: https://en.wikipedia.org/wiki).

Figure 2

Innovative technologies for natural product drug discovery. Application of these technologies can potentially lead to novel drug candidates from natural products.

Figure 3

Exploiting the properties of plant extracts in the development of novel medicines inspired by compounds found in medicinal plant extracts.

Figure 4

Precision therapies in oncology can be designed to only affect cancer cells. Biomarkers can be identified through next generation sequencing, gene expression profiling and proteomics. Drivers and regulators of important pathways involved in cancer cell proliferation, survival and chemoresistance can be identified. Only with this knowledge can the development of novel drugs be achieved.