A Historical Overview of Natural Products in Drug Discovery

Overview

Journal Metabolites

Publisher MDPI

Date 2014 Jun 25

PMID 24957513

Citations 497

Authors

Daniel A Dias

Sylvia Urban

Ute Roessner

Affiliations

Soon will be listed here.

Abstract

Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed.

Citing Articles

3D bioprinting for the construction of drug testing models-development strategies and regulatory concerns.

Mallya D, Gadre M, Varadharajan S, Vasanthan K Front Bioeng Biotechnol. 2025; 13:1457872.

PMID: 40028291 PMC: 11868281. DOI: 10.3389/fbioe.2025.1457872.

Computational framework for minimizing off-target toxicity in capecitabine treatment using natural compounds.

Jamal T, Ali A, Chauhan S, Singh R, Parthasarathi R Mol Divers. 2025; .

PMID: 40009148 DOI: 10.1007/s11030-025-11139-0.

Physalin F, a Potent Inhibitor of Lymphocyte Function, Is a Calcineurin Inhibitor and Has Synergistic Effect with Dexamethasone.

Silva D, Novo L, Ribeiro I, Barreto B, Opretzka L, Meira C Molecules. 2025; 30(4).

PMID: 40005226 PMC: 11858416. DOI: 10.3390/molecules30040916.

Inhibition of Kinase Activity and In Vitro Downregulation of the Protein Kinases in Lung Cancer and Cervical Cancer Cell Lines and the Identified Known Anticancer Compounds of .

Sambo T, Mathe E, Shai L, Mapfumari S, Gololo S Plants (Basel). 2025; 14(3).

PMID: 39942957 PMC: 11820244. DOI: 10.3390/plants14030395.

The beneficial effects of curcumin on aging and age-related diseases: from oxidative stress to antioxidant mechanisms, brain health and apoptosis.

He Y, Liu Y, Zhang M Front Aging Neurosci. 2025; 17:1533963.

PMID: 39906716 PMC: 11788355. DOI: 10.3389/fnagi.2025.1533963.

References

Yogeeswari P, Sriram D . Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem. 2005; 12(6):657-66. DOI: 10.2174/0929867053202214. View

Haefner B . Drugs from the deep: marine natural products as drug candidates. Drug Discov Today. 2003; 8(12):536-44. DOI: 10.1016/s1359-6446(03)02713-2. View

Chin Y, Balunas M, Chai H, Kinghorn A . Drug discovery from natural sources. AAPS J. 2006; 8(2):E239-53. PMC: 3231566. DOI: 10.1007/BF02854894. View

Gustafson K, Cardellina 2nd J, McMahon J, Gulakowski R, Ishitoya J, Szallasi Z . A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. J Med Chem. 1992; 35(11):1978-86. DOI: 10.1021/jm00089a006. View

Zjawiony J . Biologically active compounds from Aphyllophorales (polypore) fungi. J Nat Prod. 2004; 67(2):300-10. DOI: 10.1021/np030372w. View

Cox P . Saving the ethnopharmacological heritage of Samoa. J Ethnopharmacol. 1993; 38(2-3):181-8. DOI: 10.1016/0378-8741(93)90014-v. View

Urdiales J, Morata P, Nunez de Castro I, Sanchez-Jimenez F . Antiproliferative effect of dehydrodidemnin B (DDB), a depsipeptide isolated from Mediterranean tunicates. Cancer Lett. 1996; 102(1-2):31-7. DOI: 10.1016/0304-3835(96)04151-1. View

Lewis R, Bernstein M, Duncan S, Sleigh C . A comparison of capillary-scale LC-NMR with alternative techniques: spectroscopic and practical considerations. Magn Reson Chem. 2005; 43(9):783-9. DOI: 10.1002/mrc.1614. View

Farnsworth N, Akerele O, Bingel A, Soejarto D, Guo Z . Medicinal plants in therapy. Bull World Health Organ. 1985; 63(6):965-81. PMC: 2536466. View

10.

Zschocke S, Klaiber I, Bauer R, Vogler B . HPLC-coupled spectroscopic techniques (UV, MS, NMR) for the structure elucidation of phthalides in Ligusticum chuanxiong. Mol Divers. 2005; 9(1-3):33-9. DOI: 10.1007/s11030-005-1305-y. View

11.

Holwell S, Cooper P, Grosios K, Lippert 3rd J, Pettit G, Shnyder S . Combretastatin A-1 phosphate a novel tubulin-binding agent with in vivo anti vascular effects in experimental tumours. Anticancer Res. 2002; 22(2A):707-11. View

12.

Dias D, Urban S . Phytochemical studies of the southern Australian marine alga, Laurencia elata. Phytochemistry. 2011; 72(16):2081-9. DOI: 10.1016/j.phytochem.2011.06.012. View

13.

Lin Y, Schiavo S, Orjala J, Vouros P, Kautz R . Microscale LC-MS-NMR platform applied to the identification of active cyanobacterial metabolites. Anal Chem. 2008; 80(21):8045-54. PMC: 2709599. DOI: 10.1021/ac801049k. View

14.

Cardoso-Taketa A, Pereda-Miranda R, Choi Y, Verpoorte R, Villarreal M . Metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca using nuclear magnetic resonance spectroscopy and multivariate data analysis. Planta Med. 2008; 74(10):1295-301. DOI: 10.1055/s-2008-1074583. View

15.

Biao-Yi Z, Yu Y, Zeng-Liang Y . Investigation of antimicrobial model of Hemsleya pengxianensis W.J. Chang and its main active component by metabolomics technique. J Ethnopharmacol. 2008; 116(1):89-95. DOI: 10.1016/j.jep.2007.11.008. View

16.

Martin D, Blum R, Wilton J, Doto J, Galbraith H, Burgess G . Safety and pharmacokinetics of Bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers. Antimicrob Agents Chemother. 2007; 51(9):3063-6. PMC: 2043192. DOI: 10.1128/AAC.01391-06. View

17.

Ojima I . Modern natural products chemistry and drug discovery. J Med Chem. 2008; 51(9):2587-8. DOI: 10.1021/jm701291u. View

18.

McConnell O, Longley R, Koehn F . The discovery of marine natural products with therapeutic potential. Biotechnology. 1994; 26:109-74. View

19.

Wolfender J, Ndjoko K, Hostettmann K . Liquid chromatography with ultraviolet absorbance-mass spectrometric detection and with nuclear magnetic resonance spectroscopy: a powerful combination for the on-line structural investigation of plant metabolites. J Chromatogr A. 2003; 1000(1-2):437-55. DOI: 10.1016/s0021-9673(03)00303-0. View

20.

Min B, Nakamura N, Miyashiro H, Bae K, Hattori M . Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull (Tokyo). 1998; 46(10):1607-12. DOI: 10.1248/cpb.46.1607. View