Abstract
BackgroundNatural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products.MethodologyWe collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model.ConclusionsAnalysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins.
Highlights
Natural products (NPs) play an important role in drug discovery [1,2,3]
Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article
The drug-like properties basically contain four aspects which have their own limits: molecular weight should be less than 500 Da, hydrogen bond acceptors (HBA) should be less than 10, hydrogen bond donors (HBD) should be less than 5, partition coefficient AlogP should be less than five
Summary
Natural products (NPs) play an important role in drug discovery [1,2,3]. Researchers have done statistics and analysis for natural products in several aspects, such as chemical diversity [15,16,17,18], property distribution [19], molecular scaffold [20,21,22], chemical space [23,24] and comparison between NPs and other compound collections [22,25,26]. Researchers seldom did comprehensive statistics on natural products and comparison between NPs and other types of compounds because it was difficult to obtain large quantity of data collection (both structures and annotations). How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products
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