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Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships.
Bioorg Med Chem. 2008 Jan 15; 16(2):658-67.BM

Abstract

Inhibition of nitric oxide (NO) production by altering the expression of induced enzymes involved is potentially an important strategy for obtaining antiinflammatory agents. In the search for hits to obtain lead compounds for new drugs of this class, 14 synthetic chalcones derived from 2,4,6-trimethoxyacetophenone were evaluated in terms of their inhibitory action, in vitro, in relation to NO production in murine macrophages of the line RAW 264.7 induced by bacterial lipopolysaccharides (LPS). All the compounds were obtained by aldolic condensation between the acetophenone and corresponding aldehydes, under basic conditions. The mean IC(50) values, calculated through dose versus inhibitory effect curves, in four independent experiments, varied between 1.34 and 27.60microM, and were compared with the positive control, compound 1400W (IC(50)=3.78microM), a highly selective inhibitor of iNOS (induced nitric oxide synthase). Eight chalcones gave mean IC(50) values less than or equal to those obtained for 1400W, which suggests that these molecules may act as inhibitors of inflammatory process. The QSAR study reveals that electron-withdrawing groups in the B-ring seem to increase the inhibition of nitrite production, mainly when in position 2. A substitution in the ortho position of the A-ring seems to be necessary for the activity.

Authors+Show Affiliations

Chiaradia LD
Universidade Federal de Santa Catarina, Departamento de Química, Campus Trindade, 88040-900 Florianópolis, SC, Brazil. louisedc@gmail.com
dos Santos R
No affiliation info available
Vitor CE
No affiliation info available
Vieira AA
No affiliation info available
Leal PC
No affiliation info available
Nunes RJ
No affiliation info available
Calixto JB
No affiliation info available
Yunes RA
No affiliation info available

MeSH

AcetophenonesAnimalsAnti-Inflammatory AgentsChalconesInhibitory Concentration 50LipopolysaccharidesMacrophagesMiceMolecular StructureNitric OxideNitric Oxide Synthase Type IIQuantitative Structure-Activity Relationship

Pub Type(s)

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

Language

eng

PubMed ID

17988874

Citation

Chiaradia, Louise Domeneghini, et al. "Synthesis and Pharmacological Activity of Chalcones Derived From 2,4,6-trimethoxyacetophenone in RAW 264.7 Cells Stimulated By LPS: Quantitative Structure-activity Relationships." Bioorganic & Medicinal Chemistry, vol. 16, no. 2, 2008, pp. 658-67.
Chiaradia LD, dos Santos R, Vitor CE, et al. Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships. Bioorg Med Chem. 2008;16(2):658-67.
Chiaradia, L. D., dos Santos, R., Vitor, C. E., Vieira, A. A., Leal, P. C., Nunes, R. J., Calixto, J. B., & Yunes, R. A. (2008). Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships. Bioorganic & Medicinal Chemistry, 16(2), 658-67.
Chiaradia LD, et al. Synthesis and Pharmacological Activity of Chalcones Derived From 2,4,6-trimethoxyacetophenone in RAW 264.7 Cells Stimulated By LPS: Quantitative Structure-activity Relationships. Bioorg Med Chem. 2008 Jan 15;16(2):658-67. PubMed PMID: 17988874.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships. AU - Chiaradia,Louise Domeneghini, AU - dos Santos,Rodrigo, AU - Vitor,Carlos Eduardo, AU - Vieira,André Alexandre, AU - Leal,Paulo César, AU - Nunes,Ricardo José, AU - Calixto,João Batista, AU - Yunes,Rosendo Augusto, Y1 - 2007/10/18/ PY - 2007/08/30/received PY - 2007/10/11/revised PY - 2007/10/15/accepted PY - 2007/11/9/pubmed PY - 2008/2/21/medline PY - 2007/11/9/entrez SP - 658 EP - 67 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 16 IS - 2 N2 - Inhibition of nitric oxide (NO) production by altering the expression of induced enzymes involved is potentially an important strategy for obtaining antiinflammatory agents. In the search for hits to obtain lead compounds for new drugs of this class, 14 synthetic chalcones derived from 2,4,6-trimethoxyacetophenone were evaluated in terms of their inhibitory action, in vitro, in relation to NO production in murine macrophages of the line RAW 264.7 induced by bacterial lipopolysaccharides (LPS). All the compounds were obtained by aldolic condensation between the acetophenone and corresponding aldehydes, under basic conditions. The mean IC(50) values, calculated through dose versus inhibitory effect curves, in four independent experiments, varied between 1.34 and 27.60microM, and were compared with the positive control, compound 1400W (IC(50)=3.78microM), a highly selective inhibitor of iNOS (induced nitric oxide synthase). Eight chalcones gave mean IC(50) values less than or equal to those obtained for 1400W, which suggests that these molecules may act as inhibitors of inflammatory process. The QSAR study reveals that electron-withdrawing groups in the B-ring seem to increase the inhibition of nitrite production, mainly when in position 2. A substitution in the ortho position of the A-ring seems to be necessary for the activity. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/17988874/Synthesis_and_pharmacological_activity_of_chalcones_derived_from_246_trimethoxyacetophenone_in_RAW_264_7_cells_stimulated_by_LPS:_quantitative_structure_activity_relationships_ DB - PRIME DP - Unbound Medicine ER -