Plants for millennia have provided the major source of the medicinal compounds used to treat our illnesses. Until the early 1900’s plant-derived pharmaceuticals, primarily as preparations of mixtures derived directly from plant material, represented the major source of pharmaceuticals throughout the world. Even today, according to the World Health Organization (WHO), roughly two-thirds to
three-quarters of the world’s population relies upon medicinal plant preparations for their primary health care needs. The recognition of the importance of active ingredients in these complex mixtures fostered the development of organic chemistry, physiology, and pharmacology as important contributors to the practice of medicine. With the isolation and characterization of the structures of select natural products, synthetic organic chemistry became an important contributor to
pharmaceuticals and a number of important pharmaceuticals modeled upon natural products began to be developed. The development of aspirin based upon the salicylic acid of willow bark is a classic example.
Testing of numerous chemical compounds against an important parasitic disease and observation of efficacy led Paul Ehrlich to postulate “the Magic Bullet” concept in the early twentieth century [1,2]. In the 1930s, the observation that microorganisms produced substances which inhibited the growth and development of other microorganisms triggered the “Age of Antibiotics” and their use in medicine [3]. These naturally occurring substances had a profound impact upon
humankind through the adequate treatment of infectious diseases, formerly a major cause of early mortality in humans. Consequently, significant increases in life span have occurred over the last 100 years. The efficacy and safety of these newly discovered medicaments further solidified our belief in the magic bullet paradigm [4]. The utilization of microorganism fermentation to produce natural products for
application in medicine and the growing sophistication of synthetic organic chemistry largely displaced interest in plant-derived substances as pharmaceuticals in the 1940s through the 1980s. Importantly, the ease of standardization of single chemical entities into dosage forms, thereby allowing predictable outcomes of dosing, further supported the move to such pharmaceutical preparations. Even so, the importance of naturally derived substances for drug discovery and development was still strongly evidenced by the analysis published by Newman and Cragg in 2012 [5].
Interest in the study of plant-derived natural products is relegated to the academic community. However, the National Cancer Institute of the United States retained a core program of research on plant-derived natural products for the discovery and development of anti-cancer pharmaceuticals. The discovery and development of Taxol (Paclitaxel) in the decades of 1960s-1990s, as the most successful anti-cancer agent ever, caused a momentary resurgence of interest in natural products for drug discovery [6]. This interest has once more been replaced by a focus on new approaches to drug discovery such as combinational chemistry and computer-based molecular modeling coupled to highthroughput screening of bio-molecular models (receptors, enzymes, etc.) and most recently by our increased understanding of molecular genetics and immunology. The importance of plant-derived natural products within the pharmaceutical industry has waned significantly
over the decades from the discovery of antibiotics and has practically disappeared today.
The emergence of resistance to single chemical entity agent materials whether a pharmaceutical (antibiotic-resistant infections, drug-resistant malaria, drug-resistant tuberculosis, numerous others), insecticide (insecticide-resistant mosquitoes and crop pests), or herbicide (herbicide-resistant weeds in our crops) has or is bringing
the magic bullet paradigm into question [7]. There is an urgent need to identify novel active leads for the development of a new strategy to overcome the emergence of resistance. As was dramatically illustrated by the discovery of the “wonder” antibiotics of the 1940s and 1950s and the anticancer agent paclitaxel and others in the 1950s through the 970s, nature is the prime source of such unique, novel lead discoveries. As emphasized by Dr. Norman Farnsworth, a leading world-renowned natural product researcher, “The World of Plants, and indeed all natural sources, represents a virtually untapped reservoir of novel drugs
awaiting imaginative progressive companies [8]. The role of plant derived natural products in the discovery of prototype pharmaceuticals arises from the observation that plants interact with their environment by chemical means. Plants protect themselves; attract pollinators, etc. by means of chemical substances. Those interactions are very effective. Since plants are rooted in place, they have evolved mechanisms to protect themselves by producing chemical defense substances.
Source: Pharmaceut Reg Affairs 2019, 8:2