Creating and screening natural product libraries

Abstract

The National Cancer Institute of the United States (NCI) has initiated a Cancer Moonshot program entitled the NCI Program for Natural Product Discovery.

Sprouts and Microgreens: Trends, Opportunities, and Horizons for Novel Research

“…Thirdly, the systematic investigation of sprouts in drug discovery programs can be strongly facilitated by major advances in the production of natural product collections [293]; these include, for example, methods of sample extraction, pre-fractionation and drug-like enrichment [294][295][296]; NMR, MS and related hyphenated techniques for dereplication and unambiguous identification of novel chemicals [297][298][299]; effective and versatile solutions in high-throughput technologies [300,301]; design, optimization, and miniaturization of cell-free and cell-based screening assays [293]; and, finally, progressively easier access to integrated omics platforms applicable, for example, to target identification programs and mechanistic elucidation of a drug's biological impact, efficacy, and side or adverse effects [302] (Figure 1). investigation of biosynthetic gene clusters in plants using sequencing technologies, bioinformatics tools, and predictive computational solutions [287][288][289][290][291] is a rapidly expanding field leading towards unprecedented possibilities for tapping into unexplored metabolic pathways, identifying new molecules, and uncovering mechanisms of metabolic diversification.…”

“…In this regard, the dynamic rearrangement of neighboring genes was recently shown in Brassicaceae to rewire triterpene biosynthesis and, consequently, account for triterpene metabolic diversity [292]. Thirdly, the systematic investigation of sprouts in drug discovery programs can be strongly facilitated by major advances in the production of natural product collections [293]; these include, for example, methods of sample extraction, pre-fractionation and drug-like enrichment [294][295][296]; NMR, MS and related hyphenated techniques for dereplication and unambiguous identification of novel chemicals [297][298][299]; effective and versatile solutions in high-throughput technologies [300,301]; design, optimization, and miniaturization of cell-free and cell-based screening assays [293]; and, finally, progressively easier access to integrated omics platforms applicable, for example, to target identification programs and mechanistic elucidation of a drug's biological impact, efficacy, and side or adverse effects [302] (Figure 1). It is emblematic that in-vitro and in-vivo studies have almost exclusively been carried out using whole sprouts or, at best, fractionated extracts performed by non-standardized protocols [27,241].…”

A unique high-diversity natural product collection as a reservoir of new therapeutic leads

“…Indeed, alkaloids are characterized by their great structural diversity, as a result of which there is no uniform classification of these compounds. Oxyskitanthine (24) and dehydroskitanthine (25), which are piperidine derivatives that possess two C-methyl functional groups and one N-methyl group, were isolated for the first time from Skytunthus acutus, a Chilean member of the family Apocynaceae. 56 19-OH-coronaridina (26) and leiocarpol (27), which are both indole alkaloids, were isolated from Ervatamia coronaria 57 (family Apocynaceae) and Esembeckia leiocarpa 58 (family Rutaceae), respectively.…”

“…Today, an important challenge is the generation of high-quality libraries of natural products that might enable the rapid identification of lead compounds for drug discovery progression. 10,[20][21][22][23][24][25] In addition, the advent of powerful and user-friendly tools for informatics applications in chemistry and biology has further promoted the revolution of natural products screening in drug discovery. [26][27][28] Moreover, knowledge of the metabolic profile of a biological matrix is a powerful tool for driving investigations of its properties.…”

Identification of Putative Non-Substrate-Based XT-I Inhibitors by Natural Product Library Screening

“…Natural products (NPs) are the earliest forms of human medicine with strong, unique, anti-inflammatory, anticancer or neuroprotective properties [ 31 , 32 ]. The NPs are often more efficient than artificially made compounds if a specific biological activity, such as an enzyme inhibitor, is needed.…”