Abstract
Natural products have a significant role in drug discovery. Natural products have distinctive chemical structures that have contributed to identifying and developing drugs for different therapeutic areas. Moreover, natural products are significant sources of inspiration or starting points to develop new therapeutic agents. Natural products such as peptides and macrocycles, and other compounds with unique features represent attractive sources to address complex diseases. Computational approaches that use chemoinformatics and molecular modeling methods contribute to speed up natural product-based drug discovery. Several research groups have recently used computational methodologies to organize data, interpret results, generate and test hypotheses, filter large chemical databases before the experimental screening, and design experiments. This review discusses a broad range of chemoinformatics applications to support natural product-based drug discovery. We emphasize profiling natural product data sets in terms of diversity; complexity; acid/base; absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties; and fragment analysis. Novel techniques for the visual representation of the chemical space are also discussed.
Highlights
Natural products (NPs), from either terrestrial or aquatic organisms, have a long tradition as sources of active compounds for health-related benefits
Examples of unaltered NPs recently approved for clinical use are (Figure 1) angiotensin II acetate approved by the US Food and Drug Administration (FDA) in 2017 as a vasoconstrictor to increase blood pressure in adults with septic or other distributive shock [2]; aplidine, a new marine-derived anticancer agent approved for the first time in 2018 in Australia for the treatment of multiple myeloma [3]; and cannabidiol, approved in 2018 by the FDA as an antiepileptic drug [4]
Regarding NP derivatives, in 2019 the FDA approved nine drugs derived from NPs; among them are lefamulin used as an antibiotic, brexanolone an anti-depressant, and siponimod fumarate used to treat multiple sclerosis [1]
Summary
Natural products (NPs), from either terrestrial or aquatic organisms, have a long tradition as sources of active compounds for health-related benefits. Regarding NP derivatives, in 2019 the FDA approved nine drugs derived from NPs; among them are lefamulin used as an antibiotic, brexanolone an anti-depressant, and siponimod fumarate used to treat multiple sclerosis [1]. There are efforts to make databases of fragments derived from NPs for NP-based fragment-based drug discovery and the generation of “pseudo-NPs” publicly available [21]. Chávez-Hernández et al recently reported a large fragment library with nearly 206,000 fragments derived from a drug-like subset of the Collection of Open Natural Products (COCONUT) database. The fragment library of NPs was made freely available [22]
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