Natural products in drug discovery: advances and opportunities

被引:3228
作者
Atanasov, Atanas G. [1 ,2 ,3 ,4 ]
Zotchev, Sergey B. [2 ]
Dirsch, Verena M. [2 ]
Supuran, Claudiu T. [5 ]
机构
[1] Polish Acad Sci, Inst Genet & Anim Biotechnol, Jastrzebiec, Poland
[2] Univ Vienna, Dept Pharmacognosy, Vienna, Austria
[3] Bulgarian Acad Sci, Inst Neurobiol, Sofia, Bulgaria
[4] Med Univ Vienna, Ludwig Boltzmann Inst Digital Hlth & Patient Safe, Vienna, Austria
[5] Univ Firenze, NEUROFARBA Dept, Sez Sci Farmaceut, Florence, Italy
基金
英国生物技术与生命科学研究理事会; 瑞士国家科学基金会; 奥地利科学基金会; 欧盟地平线“2020”; 新加坡国家研究基金会; 英国医学研究理事会; 英国工程与自然科学研究理事会; 澳大利亚研究理事会; 美国国家卫生研究院;
关键词
REMITTING MULTIPLE-SCLEROSIS; BIOSYNTHETIC GENE CLUSTERS; RELEASE DIMETHYL FUMARATE; MASS-SPECTROMETRY; SECONDARY METABOLITES; LIQUID-CHROMATOGRAPHY; GUT MICROBIOTA; ANTIDIABETIC CONSTITUENTS; HETEROLOGOUS PRODUCTION; MOLECULAR NETWORKING;
D O I
10.1038/s41573-020-00114-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:200 / 216
页数:17
相关论文
共 223 条
[51]   Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress [J].
Dinkova-Kostova, AT ;
Liby, KT ;
Stephenson, KK ;
Holtzclaw, WD ;
Gao, XQ ;
Suh, N ;
Williarrli, C ;
Risingsong, R ;
Honda, T ;
Gribble, GW ;
Sporn, MB ;
Talalay, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (12) :4584-4589
[52]   Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates [J].
Doak, Bradley Croy ;
Over, Bjorn ;
Giordanetto, Fabrizio ;
Kihlberg, Jan .
CHEMISTRY & BIOLOGY, 2014, 21 (09) :1115-1142
[53]   Deep Venomics Reveals the Mechanism for Expanded Peptide Diversity in Cone Snail Venom [J].
Dutertre, Sebastien ;
Jin, Ai-hua ;
Kaas, Quentin ;
Jones, Alun ;
Alewood, Paul F. ;
Lewis, Richard J. .
MOLECULAR & CELLULAR PROTEOMICS, 2013, 12 (02) :312-329
[54]   Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics [J].
Earl, David C. ;
Ferrell, P. Brent, Jr. ;
Leelatian, Nalin ;
Froese, Jordan T. ;
Reisman, Benjamin J. ;
Irish, Jonathan M. ;
Bachmann, Brian O. .
NATURE COMMUNICATIONS, 2018, 9
[55]   Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China [J].
Egner, Patricia A. ;
Chen, Jian-Guo ;
Zarth, Adam T. ;
Ng, Derek K. ;
Wang, Jin-Bing ;
Kensler, Kevin H. ;
Jacobson, Lisa P. ;
Munoz, Alvaro ;
Johnson, Jamie L. ;
Groopman, John D. ;
Fahey, Jed W. ;
Talalay, Paul ;
Zhu, Jian ;
Chen, Tao-Yang ;
Qian, Geng-Sun ;
Carmella, Steven G. ;
Hecht, Stephen S. ;
Kensler, Thomas W. .
CANCER PREVENTION RESEARCH, 2014, 7 (08) :813-823
[56]   Significance of Microbiota in Obesity and Metabolic Diseases and the Modulatory Potential by Medicinal Plant and Food Ingredients [J].
Eid, Hoda M. ;
Wright, Michelle L. ;
Kumar, N. V. Anil ;
Qawasmeh, Abdel ;
Hassan, Sherif T. S. ;
Mocan, Andrei ;
Nabavi, Seyed M. ;
Rastrelli, Luca ;
Atanasov, Atanas G. ;
Haddad, Pierre S. .
FRONTIERS IN PHARMACOLOGY, 2017, 8
[57]  
Eugster PJ, 2011, J AOAC INT, V94, P51
[58]   Property distributions: Differences between drugs, natural products, and molecules from combinatorial chemistry [J].
Feher, M ;
Schmidt, JM .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2003, 43 (01) :218-227
[59]   Cornerstones of CRISPR-Cas in drug discovery and therapy [J].
Fellmann, Christof ;
Cowen, Benjamin C. ;
Lin, Pei-Chun ;
Doudna, Jennifer A. ;
Corn, Jacob E. .
NATURE REVIEWS DRUG DISCOVERY, 2017, 16 (02) :89-100
[60]   Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM [J].
Fernandez, Oscar ;
Giovannoni, Gavin ;
Fox, Robert J. ;
Gold, Ralf ;
Phillips, J. Theodore ;
Potts, James ;
Okwuokenye, Macaulay ;
Marantz, Jing L. .
CLINICAL THERAPEUTICS, 2017, 39 (08) :1671-1679