Underexplored Opportunities for Natural Products in Drug Discovery

Abstract

The importance of natural products in the treatment of human disease is well documented. While natural products continue to have a profound impact on human health, chemists have succeeded in generating semisynthetic analogues that sometimes overshadow the original natural product in terms of clinical significance. Synthetic efforts based on natural products have primarily focused on improving their drug-like features while targeting utility in the same biological space. A less documented phenomenon is that natural products can serve as powerful starting materials to generate drug substances with novel therapeutic utility that is unrelated to the biological space of the natural product starting material. In this Perspective, examples of natural product derived marketed drugs with therapeutic utility in clinical space that is different from the biological profile of the starting material are presented, demonstrating that this is not merely a theoretical concept but both a clinical reality and an underexplored opportunity.

Quantitative and Systems Pharmacology. 1.In SilicoPrediction of Drug–Target Interactions of Natural Products Enables New Targeted Cancer Therapy

“…1–3 Recent studies have suggested that Food and Drug Administration (FDA)-approved or clinically investigational natural products often target multiple proteins, called polypharmacology. 4 However, polypharmacology of natural products are characterized with both therapeutic effects and unwanted adverse effects.…”

The Phytochemistry of Cherokee Aromatic Medicinal Plants

“…Several plant-derived drugs are in use today, including, for example, vinblastine (from Catharanthus roseus (L.) G. Don, used to treat childhood leukemia); paclitaxel (from Taxus brevifolia Nutt., used to treat ovarian cancer); morphine (from Papaver somniferum L., used to treat pain); and quinine (from Cinchona spp., used to treat malaria) [5]. Not only are phytochemicals useful medicines in their own right, but compounds derived from them or inspired by them have become useful medicines [6,7]. For example, Artemisia annua L., a plant originally used in Traditional Chinese Medicine to treat fever, is the source of artemisinin, a clinically-useful antimalarial sesquiterpenoid [8]; the antihypertensive drug reserpine, isolated from the roots of Rauvolfia serpentina (L.) Benth.…”

A Deep Learning Genome-Mining Strategy Improves Biosynthetic Gene Cluster Prediction

“…These include multiple classes of antibacterials, as well as oncology drugs, diabetes drugs, hypocholesterolemic drugs, and immunomodulatory agents 1,2 . The global rise in antibiotic resistance 3,4 , the increased promise of immunomodulatory agents in cancer treatment 5 , and the continued need for development of new drugs across novel and complex biology is contingent upon the identification of structurally diverse bioactive compounds [6][7][8] .…”