Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives

• Published in: Bioorganic & medicinal chemistry letters 2021-03, Vol.35, p.127827-127827, Article 127827
• Main Authors: Ngameni, Bathélémy, Cedric, Kamdoum, Mbaveng, Armelle T., Erdoğan, Musa, Simo, Ingrid, Kuete, Victor, Daştan, Arif
• Format: Article
• Language: English
• Subjects: 4-O-substituted chalcones; 4-O-substituted phenylcarbonyls; Anticancer activity; Claisen-Schmidt condensation; Nucleophilic O-substitution reaction; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.127827

[Display omitted] •Seventeen new chalcone derivates were designed and synthesized.•Structures of these compounds were fully characterized.•Interesting products were obtained as prochiral chalcones.•The newly synthesized compounds have a promising potential for the future development of active anticancer agents. A new series of O-substituted chalcone derivatives bearing an/a allyl-, prenyl- or propargyl-substituent at different positions of rings A and B and their derivatives as drug leads, was designed, synthesized, and characterized. The chalcone derivatives were synthesized via base catalyzed Claisen-Schmidt condensation in MeOH or EtOH solutions of appropriately substituted aromatic ketones with O-allyl, and O-propargylvanillin, respectively. The intermediates O-substituted phenylketone derivatives were firstly synthesized by nucleophilic substitution reaction. All the newly synthesized compounds were characterized by IR, NMR spectral data and elemental analyses. A preliminary cytotoxicity was performed with the compounds (1a, 1b, 2a, 2b, 3a, 3b, 4a, 5a-f, 6a-d, 7a-d) and the positive control, doxorubicin towards CCRF-CEM leukemia cells. Amongst them, compounds 1a, 2a, 5b-d, 6b, 7a, 7c and doxorubicin displayed IC50 values below 20 µM while other compounds were less or not active at up to 50 µM. Remarkably interesting cytotoxic effects, with IC50 values below 1 µM were recorded with 5c against HCT116 p53-/- colon adenocarcinoma cells, 5e against CCRF-CEM cells and MDA-MB-231-BCRP breast adenocarcinoma cells, and 6b against HCT116 p53+/+ cells and HCT116 p53-/- cells.