Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 28;27(3):886.
doi: 10.3390/molecules27030886.

Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides

Amandeep Singh  1 , Asif Raza  1 , Shantu Amin  1 , Chendil Damodaran  2 , Arun K Sharma  1
Affiliations
Review

Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides

Amandeep Singh et al. Molecules. .

Abstract

Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.

Keywords: anti-bacterial; anti-inflammatory; anti-leishmaniasis; anticancer; withaferin A; withanolides.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Figures

Figure 1
Figure 1
Structure of Withaferin A (WA, 1) and its reactive sites exploited for structural modifications.
Figure 2
Figure 2
Withanolides isolated from P. angulata.
Figure 3
Figure 3
Withanolides isolated from P. alkekengi.
Figure 4
Figure 4
Withanolides isolated from P. longifolia.
Figure 5
Figure 5
Withanolides isolated from P. neomaxicana.
Figure 6
Figure 6
Withanolides isolated from P. crassifolia.
Figure 7
Figure 7
Withanolides isolated from P. pubescens L.
Figure 8
Figure 8
Withanolides isolated from P. peruviana.
Figure 9
Figure 9
Withanolides isolated from genus Datura.
Figure 10
Figure 10
Withanolides isolated from genus Withania.
Figure 11
Figure 11
Withanolides isolated from Dioscorea japonica 78–79, Sinularia brassica 80–86, and Tacca plantaginea 87–90.
Figure 12
Figure 12
Withanolides isolated from Acnistus arborescens (91–94), Tubocapsicum anomalum (95–99), and Eriolarynx and Deprea (100–103).
Figure 13
Figure 13
Withanolides isolated from Sonoran desert plants.
Figure 14
Figure 14
Monosubstituted analogs of WA.
Figure 15
Figure 15
Disubstituted analogs of WA.
Figure 16
Figure 16
Trisubstituted analogs of WA and related mono- and di-substituted compounds studied for comparison.
Figure 17
Figure 17
Fused analogs of WA.
Figure 18
Figure 18
Common synthetic features of withanolide analogs.
Figure 19
Figure 19
Most potent withanolides from Minabea sp.
Figure 20
Figure 20
Withanolides isolated from D. metel L.
Figure 21
Figure 21
Withanolides isolated from P. minima.
Figure 22
Figure 22
Withanolides isolated from Sinularia brassica.
Figure 23
Figure 23
Withanolides isolated from N. physaloides and S. capsicoides.
Figure 24
Figure 24
Withanolides isolated from D. metel L.
Figure 25
Figure 25
Withanolides isolated from Nicandra Adans.
Figure 26
Figure 26
Withanolides isolated from W. coagulanes.
See this image and copyright information in PMC

References

    1. Newman D.J., Cragg G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020;83:770–803. doi: 10.1021/acs.jnatprod.9b01285. - DOI - PubMed
    1. Cragg G.M., Grothaus P.G., Newman D.J. New Horizons for Old Drugs and Drug Leads. J. Nat. Prod. 2014;77:703–723. doi: 10.1021/np5000796. - DOI - PubMed
    1. Newman D.J., Cragg G.M. Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod. 2016;79:629–661. doi: 10.1021/acs.jnatprod.5b01055. - DOI - PubMed
    1. Barreca M., Spanò V., Montalbano A., Cueto M., Díaz Marrero A.R., Deniz I., Erdoğan A., Lukić Bilela L., Moulin C., Taffin-de-Givenchy E. Marine anticancer agents: An overview with a particular focus on their chemical classes. Mar. Drugs. 2020;18:619. doi: 10.3390/md18120619. - DOI - PMC - PubMed
    1. Cragg G.M., Newman D.J. Natural products: A continuing source of novel drug leads. Biochim. Biophys. Acta. 2013;1830:3670–3695. doi: 10.1016/j.bbagen.2013.02.008. - DOI - PMC - PubMed

MeSH terms