Synthetic chalcones, flavanones, and flavones as antitumoral agents: Biological evaluation and structure–activity relationships

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 10; pp. 3356 - 3367
• Main Authors: Cabrera, Mauricio, Simoens, Macarena, Falchi, Gabriela, Lavaggi, M. Laura, Piro, Oscar E., Castellano, Eduardo E., Vidal, Anabel, Azqueta, Amaia, Monge, Antonio, de Ceráin, Adela López, Sagrera, Gabriel, Seoane, Gustavo, Cerecetto, Hugo, González, Mercedes
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.05.2007; Elsevier Science
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antitumoral; Biological and medical sciences; Cell Line, Tumor; Chalcones - chemical synthesis; Chalcones - pharmacology; Chromatography, Thin Layer; Chromosome Aberrations - drug effects; Comet Assay; DNA Damage; DNA, Neoplasm - drug effects; Drug Screening Assays, Antitumor; Flavones - chemical synthesis; Flavones - pharmacology; Flavonoids; General aspects; Humans; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Pharmacology. Drug treatments; QSAR; Spectrophotometry, Infrared; Structure-Activity Relationship; X-Ray Diffraction; Flavonoids; Antitumoral; QSAR; Comet assay; Antineoplastic agent; Human; Molecular structure; Mutagenicity testing; Toxicity; Cytotoxicity; Mutagen; X ray diffraction; Flavonoid; In vitro; Kidney; Flavanone derivatives; Cell line; Structure activity relation; Flavone derivatives; Colon; Mammary gland; Chemical synthesis; Tumor cell; Crystalline structure
• DOI: 10.1016/j.bmc.2007.03.031
• ISSN: 0968-0896

A wide series of synthetic flavonoids, with druglikeness properties, were developed and evaluated as antitumoral agents against TK-10, MCF-7, and HT-29 human tumoral cells. Comet assay was performed against non-tumoral HK-2 in order to know chromosomal aberrations in normal cells. A QSAR was obtained for anti-HT-29 activities. A series of synthetic chalcones, flavanones, and flavones has been synthesized and evaluated for antitumor activity against the human kidney carcinoma cells TK-10, human mammary adenocarcinoma cells MCF-7 (estrogen receptor-positive), and human colon adenocarcinoma cells HT-29. The most active series is the chalcone ones with the best results against TK-10 and HT-29 cells. Fourteen out of 53 analyzed compounds resulted very active against at least two of the studied tumoral cells. Alkaline single cell gel electrophoresis, comet assay, was performed as a study of the chromosomal aberrations promoted by the compounds on normal cells. Four active and two inactive chalcones were studied in the comet assay against normal human kidney cells (HK-2). A structure–activity relationship analysis of these compounds was performed and for 4- and 3,4-disubstituted derivatives a quantitative correlation was obtained in the case of anti-HT-29 activity.