Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays

Abstract

Natural extracts are complex mixtures that may be rich in useful bioactive compounds and therefore are attractive sources for new leads in drug discovery. This review describes drug discovery from natural products and in explaining this process puts the focus on ion-channel drug discovery. In particular, the identification of bioactives from natural products targeting nicotinic acetylcholine receptors (nAChRs) and serotonin type 3 receptors (5-HT3Rs) is discussed. The review is divided into three parts: “Targets,” “Sources,” and “Approaches.” The “Targets” part will discuss the importance of ion-channel drug targets in general, and the α7-nAChR and 5-HT3Rs in particular. The “Sources” part will discuss the relevance for drug discovery of finding bioactive compounds from various natural sources such as venoms and plant extracts. The “Approaches” part will give an overview of classical and new analytical approaches that are used for the identification of new bioactive compounds with the focus on targeting ion channels. In addition, a selected overview is given of traditional venom-based drug discovery approaches and of diverse hyphenated analytical systems used for screening complex bioactive mixtures including venoms.

Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety

“…The best record of using natural extracts in therapy is the Egyptians' Ebers Papyrus (from 1500 BCE), which documents more than 700 natural drugs, mainly of plant origin. The Chinese Materia Medica record (BCE 1100) describes 52 natural medicinal preparations, and the Indian Ayurvedic record (BCE 1000) describes more than 800 natural medicinal extracts (Cragg and Newman, 2013;Otvos et al, 2019). Hippocrates also applied phytotherapy, or healing with herbs, in his treatments (Otvos et al, 2019).…”

“…Despite the many successes of using natural products for drug production, advances in combinatorial chemistry (in the late 1980s) shifted the focus of drug discovery efforts from natural products to synthesis at the laboratory bench (Cragg and Newman, 2013). This is mainly because natural product-based drug discovery and development is a complex endeavor demanding costly and highly integrated interdisciplinary approaches (Davison and Brimble, 2019;Otvos et al, 2019). Nonetheless, currently the use of natural products as drugs or as drug discovery platforms is "well and alive" (Newman and Cragg, 2016).…”

“…Numerous and chemically diverse secondary metabolites have been purified from plant bioactives and have been optimized for exerting a biological effect, nonetheless, they are still away from exhaustive investigation for clinical use. However, recent published scientific evidence, technological advances, and research trends clearly point that naturally-derived compounds will be major sources of new drugs (Davison and Brimble, 2019;Otvos et al, 2019). This has provided a driving cause for the renewed popularity of traditional herbal and plant-derived medications among researchers, despite developments in combinatorial chemical synthesis and the production of modern synthetic drugs (Frishman et al, 2009).…”

Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model

“…Traditional medicines are naturally derived from plant bioactive substances with minimal or no industrial processing. They have been used to cure or prevent illness within local or regional healing practices [ 24 ]. This work was design to evaluate toxicity and anticholinesterase effect of Ginkgo biloba 80% methanolic seed extract.…”

Label‐free Bio‐affinity Mass Spectrometry for Screening and Locating Bioactive Molecules

“…Natural product extracts have become one of the most important sources of new drugs. Many advances have been made in the development of the BA‐MS method facilitating the identification of bioactive compounds from natural products (Potterat & Hamburger, 2013; Otvos et al, 2019). Yang et al (2016) employed electrospray ionization Fourier transform ion cyclotron resonance MS (ESI‐FT‐ICR‐MS) to screen extracts from Australian plants against a malaria target Plasmodium falciparum deoxyuridine 5′‐triphosphate nucleotidohydrolase.…”