Chalcone

Chalcone is an aromatic ketone and an enone that forms the central core for a variety of important biological compounds, which are known collectively as chalcones or chalconoids. Alternative names for chalcone include benzylideneacetophenone, phenyl styryl ketone, benzalacetophenone, β-phenylacrylophenone, γ-oxo-α,γ-diphenyl-α-propylene, and α-phenyl-β-benzoylethylene.

Chalcone[1]
Names
Preferred IUPAC name
Chalcone[2]
Systematic IUPAC name
(2E)-1,3-Diphenylprop-2-en-1-one
Other names
Chalkone
Benzylideneacetophenone
Phenyl styryl ketone
Identifiers
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.002.119
PubChem CID
CompTox Dashboard (EPA)
Properties
Chemical formula
 C15H12O
Molar mass 208.260 g·mol−1
Density 1.071 g/cm3
Melting point 55 to 57 °C (131 to 135 °F; 328 to 330 K)
Boiling point 345 to 348 °C (653 to 658 °F; 618 to 621 K)
Magnetic susceptibility (χ)
 -125.7·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Chemical properties

Chalcones have two absorption maximums at 280 nm and 340 nm.[3]

Chemical reactions

Synthesis

Chalcones can be prepared by an aldol condensation between benzaldehyde and acetophenone in the presence of sodium hydroxide as a catalyst.[4][5]

This reaction can be carried out without any solvent as a solid-state reaction.[6] The reaction between substituted benzaldehydes and acetophenones can be used as an example of green chemistry in undergraduate education.[7] In a study investigating green syntheses, chalcones were synthesized from the same starting materials in high-temperature water (200 to 350 °C).[8]

Substituted chalcones were also synthesised by piperidine-mediated condensation to avoid side reactions such as multiple condensations, polymerizations, and rearrangements.[9]

Other reactions

An example is the conjugate reduction of the enone by tributyltin hydride:[10]

3,5-Disubstituted 1H-pyrazoles can be produced from a suitably substituted chalcone by reaction with hydrazine hydrate in the presence of elemental sulfur[11] or sodium persulfate,[12] or by using a hydrazone in which case an azine is produced as a by-product. The specific case for formation of 3,5-diphenyl-1H-pyrazole from chalcone itself can be represented as:[13]

Potential pharmacology

Chalcones and their derivatives demonstrate a wide range of biological activities including anti-inflammation.[14] Some 2′-amino chalcones are have been studied as potential antitumor agents.[15][16] The therapeutic (anti-cancer, anti-bacterial, anti-fungal, anti-viral, anti-ameobic, anti-malarial, anti-tubercular, nematicidal, anti-oxidant, inhibitors against various therapeutic targets, etc.), catalytic, chemosensing, and photosensitizing potentials of various Metal (Iron, Ruthenium, Platinum, Copper, Zinc, Cobalt, Manganese, Nickel, Osmium, Chromium, Tellurium, Boron, Tungsten, and Silicon)-Chalcone complexes have also been reported. [17]

Biological Target Inhibition Perspectives

Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ATP-binding cassette super-family G member 2 (ABCG2), P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, histone deacetylase (HDAC)/Sirtuin-1, proteasome, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) kinase, matrix metalloproteinases (MMP)-2/9, Janus kinases (JAK)/Signal transducer and activator of transcription proteins (STAT) signaling pathways, Cell Division Cycle-25 (CDC25B), tubulin, cathepsin-K, topoisomerase-II, Wingless-related integration site (Wnt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), v-raf murine sarcoma viral oncogene homolog B1 (B-Raf), mammalian target of rapamycin (mTOR), etc. [18] Chalcone molecules deserve the credit of being potential anti-diabetic candidates that act by modulating the therapeutic targets Peroxisome proliferator-activated receptor gamma (PPAR-Γ), Dipeptidyl peptidase-4 (DPP-4), α-glucosidase, Protein-tyrosine Phosphatase 1B (PTP1B), aldose reductase, and tissue sensitivity. [19] Chalcones have been identified as the potential anti-infective candidates that inhibit various parasitic, malarial, bacterial, viral, and fungal targets like cruzain-1/2, trypanopain-Tb, trans-sialidase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fumarate reductase, falcipain-1/2, β-hematin, topoisomerase-II, plasmepsin-II, lactate dehydrogenase, protein kinases (Pfmrk and PfPK5), sorbitol-induced hemolysis, recombinant dengue virus Type 1 (DEN-1 NS3), influenza A virus (H1N1), human immunodeficiency virus (HIV-Integrase/Protease), protein tyrosine phosphatase A/B (Ptp-A/B), filamentous temperature-sensitive mutant Z (FtsZ), fatty acid syntheses (FAS-II), lactate/isocitrate dehydrogenase, NorA efflux pump, deoxyribonucleic acid (DNA) gyrase, fatty acid synthase, chitin synthase, β-(1,3)-glucan synthase, etc. [20] Chalcones are the promising candidates in inhibiting various cardiovascular, hematological and anti-obesity targets like angiotensin-converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca2+)/potassium (K+) channel, thromboxane (TXA2 and TXB2), etc. [21] Chalcone derivatives have demonstrated admirable anti-inflammatory activity due to their inhibitory potential against various therapeutic targets like cyclooxygenase (COX), lipooxygenase (LOX), interleukins (IL), prostaglandins (PGs), nitric oxide synthase (NOS), leukotriene D4 (LTD4), nuclear factor-κB (NFκB), intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), TLR4/MD-2, etc. [22]

See also
  • Juliá–Colonna epoxidation

References
  1. Merck Index, 11th Edition, 2028
  2. "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 722. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4.
  3. Song, Dong-mee; Jung, Kyoung-Hoon; Moon, Ji-hye; Shin, Dong-Myung (2003). "Photochemistry of chalcone and the application of chalcone-derivatives in photo-alignment layer of liquid crystal display". Optical Materials. 21 (1–3): 667–71. Bibcode:2003OptMa..21..667S. doi:10.1016/S0925-3467(02)00220-3.
  4. Dumitru, Sîrbu; Ion, Marin (2011). "SYNTHESIS AND IR, NMR CARACTERISATION OF NEW P-(N,N-DIPHENYLAMINO) CHALCONES". Cite journal requires |journal= (help)
  5. Gómez-Rivera, Abraham; Aguilar-Mariscal, Hidemí; Romero-Ceronio, Nancy; Roa-de la Fuente, Luis F.; Lobato-García, Carlos E. (2013-10-15). "Synthesis and anti-inflammatory activity of three nitro chalcones". Bioorganic & Medicinal Chemistry Letters. 23 (20): 5519–5522. doi:10.1016/j.bmcl.2013.08.061. ISSN 0960-894X.
  6. Toda, Fumio; Tanaka, Koichi; Hamai, Koki (1990). "Aldol condensations in the absence of solvent: Acceleration of the reaction and enhancement of the stereoselectivity". Journal of the Chemical Society, Perkin Transactions 1 (11): 3207–9. doi:10.1039/P19900003207.
  7. Palleros, Daniel R (2004). "Solvent-Free Synthesis of Chalcones". Journal of Chemical Education. 81 (9): 1345. Bibcode:2004JChEd..81.1345P. doi:10.1021/ed081p1345.
  8. Comisar, Craig M; Savage, Phillip E (2004). "Kinetics of crossed aldol condensations in high-temperature water". Green Chemistry. 6 (4): 227–31. doi:10.1039/b314622g.
  9. Venkatesan, P; Sumathi, S (2009). "Piperidine mediated synthesis ofn-heterocyclic chalcones and their antibacterial activity". Journal of Heterocyclic Chemistry. 47 (1): 81–84. doi:10.1002/jhet.268.
  10. Leusink, A.J; Noltes, J.G (1966). "Reaction of organotin hydrides with α,β-unsaturated ketones". Tetrahedron Letters. 7 (20): 2221–5. doi:10.1016/S0040-4039(00)72405-1. hdl:1874/17014.
  11. Outirite, Moha; Lebrini, Mounim; Lagrenée, Michel; Bentiss, Fouad (2008). "New one step synthesis of 3,5-disubstituted pyrazoles under microwave irradiation and classical heating". Journal of Heterocyclic Chemistry. 45 (2): 503–5. doi:10.1002/jhet.5570450231.
  12. Zhang, Ze; Tan, Ya-Jun; Wang, Chun-Shan; Wu, Hao-Hao (2014). "One-Pot Synthesis of 3,5-Diphenyl-1H-pyrazoles from Chalcones and Hydrazine under Mechanochemical Ball Milling". Heterocycles. 89: 103–12. doi:10.3987/COM-13-12867.
  13. Lasri, Jamal; Ismail, Ali I. (2018). "Metal-free and FeCl3-catalyzed synthesis of azines and 3,5-diphenyl-1H-pyrazole from hydrazones and/or ketones monitored by high resolution ESI+-MS". Indian Journal of Chemistry, Section B. 57B (3): 362–373.
  14. Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek (2017). "Chalcone Derivatives: Anti-inflammatory Potential and Molecular Targets Perspectives". Current Topics in Medicinal Chemistry. 17 (28): 3146–3169. doi:10.2174/1568026617666170914160446. PMID 28914193.
  15. Xia, Yi; Yang, Zheng-Yu; Xia, Peng; Bastow, Kenneth F.; Nakanishi, Yuka; Lee, Kuo-Hsiung (2000). "Antitumor agents. Part 202: Novel 2′-amino chalcones: design, synthesis and biological evaluation". Bioorganic & Medicinal Chemistry Letters. 10 (8): 699–701. doi:10.1016/S0960-894X(00)00072-X. ISSN 0960-894X. PMID 10782667.
  16. Santos, Mariana B.; Pinhanelli, Vitor C.; Garcia, Mayara A.R.; Silva, Gabriel; Baek, Seung J.; França, Suzelei C.; Fachin, Ana L.; Marins, Mozart; Regasini, Luis O. (2017). "Antiproliferative and pro-apoptotic activities of 2′- and 4′-aminochalcones against tumor canine cells" (PDF). European Journal of Medicinal Chemistry. 138: 884–889. doi:10.1016/j.ejmech.2017.06.049. hdl:11449/174929. ISSN 0223-5234.
  17. Mahapatra, D. K., Bharti, S. K., Asati, V., & Singh, S. K. (2017). Perspectives of medicinally privileged chalcone based metal coordination compounds for biomedical applications. European journal of medicinal chemistry, 174, 142-158. DOI: https://doi.org/10.1016/j.ejmech.2019.04.032
  18. Mahapatra, D. K., Bharti, S. K., & Asati, V. (2015). Anti-cancer chalcones: Structural and molecular target perspectives. European journal of medicinal chemistry, 98, 69-114. DOI: https://doi.org/10.1016/j.ejmech.2015.05.004
  19. Mahapatra, D. K., Asati, V., & Bharti, S. K. (2015). Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives. European journal of medicinal chemistry, 92, 839-865. DOI: https://doi.org/10.1016/j.ejmech.2015.01.051
  20. Mahapatra, D. K., Bharti, S. K., & Asati, V. (2015). Chalcone scaffolds as anti-infective agents: Structural and molecular target perspectives. European journal of medicinal chemistry, 101, 496-524. DOI: https://doi.org/10.1016/j.ejmech.2015.06.052
  21. Mahapatra, D. K., & Bharti, S. K. (2016). Therapeutic potential of chalcones as cardiovascular agents. Life sciences, 148, 154-172. DOI: https://doi.org/10.1016/j.lfs.2016.02.048
  22. Mahapatra, D. K., Bharti, S. K., & Asati, V. (2017). Chalcone derivatives: Anti-inflammatory potential and molecular targets perspectives. Current topics in medicinal chemistry, 17(28), 3146-3169. DOI: https://doi.org/10.2174/1568026617666170914160446
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