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Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect.
Eur J Med Chem. 2010 Jun; 45(6):2206-13.EJ

Abstract

Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'-dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'-trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3+/-0.4 microM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7+/-0.3 and 6.0+/-1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 microM the TNFalpha induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively.

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Authors+Show Affiliations

Vogel S
Institute of Pharmacy, Chair of Pharmaceutical Biology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
Barbic M
No affiliation info available
Jürgenliemk G
No affiliation info available
Heilmann J
No affiliation info available

MeSH

AnimalsAnti-Inflammatory AgentsAntineoplastic AgentsAntioxidantsChalconesHeLa CellsHumansInhibitory Concentration 50RatsStructure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20153559

Citation

Vogel, Susanne, et al. "Synthesis, Cytotoxicity, Anti-oxidative and Anti-inflammatory Activity of Chalcones and Influence of A-ring Modifications On the Pharmacological Effect." European Journal of Medicinal Chemistry, vol. 45, no. 6, 2010, pp. 2206-13.
Vogel S, Barbic M, Jürgenliemk G, et al. Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. Eur J Med Chem. 2010;45(6):2206-13.
Vogel, S., Barbic, M., Jürgenliemk, G., & Heilmann, J. (2010). Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. European Journal of Medicinal Chemistry, 45(6), 2206-13. https://doi.org/10.1016/j.ejmech.2010.01.060
Vogel S, et al. Synthesis, Cytotoxicity, Anti-oxidative and Anti-inflammatory Activity of Chalcones and Influence of A-ring Modifications On the Pharmacological Effect. Eur J Med Chem. 2010;45(6):2206-13. PubMed PMID: 20153559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect. AU - Vogel,Susanne, AU - Barbic,Matej, AU - Jürgenliemk,Guido, AU - Heilmann,Jörg, Y1 - 2010/01/29/ PY - 2009/11/16/received PY - 2010/01/22/revised PY - 2010/01/25/accepted PY - 2010/2/16/entrez PY - 2010/2/16/pubmed PY - 2010/7/28/medline SP - 2206 EP - 13 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 45 IS - 6 N2 - Besides 2',4'-dihydroxy-4,6'-dimethoxy-3'-prenylchalcone (1) and 4-acetoxy-2',4'-dihydroxy-6'-methoxy-3'-prenylchalkon (2), both phase II metabolites of xanthohumol in rats, also a principally new chalcone 3'-coumaroyl-2',4,4'-trihydroxy-6'-methoxychalcone (3), structurally derived from helichrysetin (4) by introducing a second coumaroyl substructure at C-3' was synthesized. Furthermore new chalcones were synthesized by combination of the B-Ring fragments of helichrysetin, xanthohumol, xanthohumol C and xanthohumol H with ferulic or caffeic acid moieties in Ring A. Compound 3 showed the highest cytotoxic activity against HeLa cells with an IC50 value of 7.3+/-0.4 microM. Anti-oxidative effects were determined in the ORAC assay and revealed very strong activity for 3 and 3-methoxyhelichrysetin (6) exhibiting 7.7+/-0.3 and 6.0+/-1.3 Trolox equivalents, respectively. The anti-inflammatory activity of all compounds was measured in an in vitro ICAM-1 assay with human microvascular endothelial cells (HMEC-1) and compared with the activity of other structurally related chalcones. The results showed increasing anti-inflammatory activity for the new synthetic chalcones exhibiting a caffeoyl substructure with 3-hydroxyhelichrysetin (5) and 3-hydroxyxanthohumol H (14) being the most active. At 10 microM the TNFalpha induced expression of ICAM-1 was significantly reduced to 65.8 and 69.6% of control, respectively. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/20153559/Synthesis_cytotoxicity_anti_oxidative_and_anti_inflammatory_activity_of_chalcones_and_influence_of_A_ring_modifications_on_the_pharmacological_effect_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(10)00105-4 DB - PRIME DP - Unbound Medicine ER -