Natural Products as Lead Compounds in Medicinal Chemistry: Opportunities and Challenges

Abstract

Natural products have attracted significant attention as the important sources of lead compounds in medicinal chemistry by virtue of their extraordinary structural diversity, biological specificity, and capacity to react with a variety of molecular targets. The review focuses on evidence obtained solely based on animal-based preclinical studies to evaluate the therapeutic potential, mechanisms of action, pharmacokinetic behavior and safety profiles of natural compounds. Results in the animal models indicate that natural products have great pharmacological activities, such as anticancer effects via the induction of apoptosis and angiogenesis inhibition, anti-inflammatory effects via suppressing pro-inflammatory cytokines and oxidative stress, antimicrobial effects against resistant pathogens, and neuroprotective effects via the regulation of neuronal signaling and inhibition of toxic Although these are encouraging results, there are various limitations that are encountered, including low bioavailability, low solubility, rapid metabolism and variability in natural sources, which collectively limit their clinical uses. Moreover, physiological differences between animal models and humans also create translational challenges to predictability of preclinical findings. To overcome such limitations, new developments in drug delivery systems, such as nanoparticle-based drug delivery systems, liposomes, and polymeric formulations, as well as structural changes, such as prodrug development, have demonstrated the possibility of improving stability and therapeutic effectiveness. In general, although natural products still have enormous potential as lead compounds, pharmacokinetic and translational challenges are critical to their effective transition into clinically useful drugs.