Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives
- Bioorg Med Chem Lett. 2021 Mar 1:35:127827. doi: 10.1016/j.bmcl.2021.127827.
- 1. Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, P.O. Box. 1364, Yaoundé, Cameroon; Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum 25240, Turkey. Electronic address: [email protected].
- 2. Department of Chemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon.
- 3. Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
- 4. Department of Food Engineering, Faculty of Engineering and Architecture, Kafkas University, Kars 36100, Turkey. Electronic address: [email protected].
- 5. Department of Chemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
- 6. Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum 25240, Turkey.
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.