title: Superior anticancer activity of halogenated chalcones and flavonols over the natural flavonol quercetin.
abstract: A series of chalcone and flavonol derivatives were synthesized in good yield by an eco-friendly approach. A pharmacological evaluation was performed with the human colorectal carcinoma cell line HCT116 and revealed that the anticancer activity of flavonols was higher when compared with that of the respective chalcone precursors. The antiproliferative activity of halogenated derivatives increases as the substituent in the 3- or 4-positon of the B-ring goes from F to Cl and to Br. In addition, halogens in position 3 enhance anticancer activity in chalcones whereas for flavonol derivatives the best performance was registered for the 4-substituted derivatives. Flow cytometry analysis showed that compounds 3p and 4o induced cell cycle arrest and apoptosis as demonstrated by increased S, G2/M and sub-G1 phases. These data were corroborated by western blot and fluorescence microscopy analysis. In summary, halogenated chalcones and flavonols were successfully prepared and presented high anticancer activity as shown by their cell growth and cell cycle inhibitory potential against HCT116 cells, superior to that of quercetin, used as a positive control.
authors.affiliation: Centre of Chemistry, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Dias
authors.forename: Cecília L
authors.initials: CL
authors.lastname: Duarte
authors.forename: Cristovao F
authors.initials: CF
authors.lastname: Lima
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Proença
authors.forename: Cristina
authors.initials: C
authors.lastname: Pereira-Wilson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D044948:Flavonols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D047188:Chalcones; D044948:Flavonols
keywords: AETKQQBRKSELEL-ZHACJKMWSA-N; AMZBRMFEFBZSCE-CMDGGOBGSA-N; Anticancer activity; BGVXUADKPAJQBF-JXMROGBWSA-N; BXLAVJWSFYZDPF-UHFFFAOYSA-N; Chalcone; Colorectal carcinoma; DCFATOGKCNMAAI-CMDGGOBGSA-N; FTMVUENCCJQCAB-UHFFFAOYSA-N; Flavonol; GBAMFFILOSWMOO-MDZDMXLPSA-N; GKEWBRFPQGHVQI-UHFFFAOYSA-N; GYLGASXCHFNKHD-UHFFFAOYSA-N; HCT116 cells; HDDWDDWMOLWPOL-MDZDMXLPSA-N; HVQAJTFOCKOKIN-UHFFFAOYSA-N; IIBBFGMVMNZMGA-UHFFFAOYSA-N; KRLBFAOXSDMNIZ-UHFFFAOYSA-N; MFLSRHQHCDTOGH-VQHVLOKHSA-N; MOKOXBWJYLCGIB-CMDGGOBGSA-N; MWFLTXAQDCOKEK-UHFFFAOYSA-N; NBYQCQSUQYBXIR-JXMROGBWSA-N; NOPCFBOJEWSFKO-UHFFFAOYSA-N; NXBNYUSXDBHELA-DHZHZOJOSA-N; OAQDOUDNROECDO-UHFFFAOYSA-N; OOEWKJHFFYCQBM-ZHACJKMWSA-N; PSEYXHGXWGGHCF-UHFFFAOYSA-N; QAHZLNKOVIYDGB-UHFFFAOYSA-N; RBCJPKVEKWAARH-JXMROGBWSA-N; SNTIPKTZVAKPOX-ZHACJKMWSA-N; SRSBUHVXNLHWHU-CMDGGOBGSA-N; UKFWQYIIRNXCEQ-MDZDMXLPSA-N; URPAREMBXBSUFI-VQHVLOKHSA-N; VEJWQQOOYBOGGJ-UHFFFAOYSA-N; VNRSYVUAUSQOIE-UHFFFAOYSA-N; XKHRVIACZOQQNZ-UHFFFAOYSA-N; YIYXRAZENVLXMP-CMDGGOBGSA-N; ZKBILMWSVPPRAT-JXMROGBWSA-N