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Natural products in drug discovery: advances and opportunities

2021; Nature Portfolio; Volume: 20; Issue: 3 Linguagem: Inglês

10.1038/s41573-020-00114-z

1474-1784

Atanas G. Atanasov, Sergey B. Zotchev, Verena M. Dirsch, İlkay Erdoğan Orhan, Maciej Banach, Judith M. Rollinger, Davide Barreca, Wolfram Weckwerth, Rudolf Bauer, Edward A. Bayer, Shaheen Majeed, Anupam Bishayee, Valery N. Bochkov, Günther K. Bonn, Nady Braidy, Franz Bučar, Alejandro Cifuentes, Grazia D’Onofrio, Michael J. Bodkin, Marc Diederich, Albena T. Dinkova‐Kostova, Thomas Efferth, Khalid El Bairi, Nicolas Arkells, Tai-Ping Fan, Bernd L. Fiebich, Michael Freissmuth, Milen I. Georgiev, Simon Gibbons, Keith M. Godfrey, Christian W. Gruber, Jag Heer, Lukas A. Huber, Elena Ibáñez, Anake Kijjoa, Anna K. Kiss, Aiping Lü, Francisco A. Macı́as, Mark J.S. Miller, Andrei Mocan, Rolf Müller, Ferdinando Nicoletti, George Perry, Valeria Pittalà, Luca Rastrelli, Michael Ristow, Gian Luigi Russo, A. Sanches‐Silva, Daniela Schuster, Helen Sheridan, Krystyna Skalicka‐Woźniak, Léandros Skaltsounis, Eduardo Sobarzo‐Sánchez, David S. Bredt, Hermann Stuppner, Antoni Sureda, Nikolay Tzvetkov, Rosa Anna Vacca, Bharat B. Aggarwal, Maurizio Battino, Francesca Giampieri, Michaël Wink, Jean-Luc Wolfender, Jianbo Xiao, Andy Wai Kan Yeung, Gérard Lizard, Michael Popp, Michael Heinrich, Ioana Ilie, Marc Stadler, Maria Daglia, Robert Verpoorte, Claudiu T. Supuran,

Phytochemical compounds biological activities

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities. Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.