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.
Department of Chemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon.
Bioorg Med Chem Lett. 2021 Mar 1;35:127827. doi: 10.1016/j.bmcl.2021.127827. Epub 2021 Jan 26.
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 IC values below 20 µM while other compounds were less or not active at up to 50 µM. Remarkably interesting cytotoxic effects, with IC 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.
设计、合成并表征了一系列新型 O-取代查耳酮衍生物，其在环 A 和环 B 的不同位置带有烯丙基、prenyl 或炔丙基取代基，以及作为药物先导的这些衍生物。查耳酮衍生物通过适当取代的芳香酮与 O-烯丙基和 O-炔丙基香草醛在 MeOH 或 EtOH 溶液中碱催化的 Claisen-Schmidt 缩合合成。中间体 O-取代苯甲酮衍生物通过亲核取代反应首先合成。所有新合成的化合物均通过 IR、NMR 光谱数据和元素分析进行了表征。用化合物（1a、1b、2a、2b、3a、3b、4a、5a-f、6a-d、7a-d）和阳性对照阿霉素对 CCRF-CEM 白血病细胞进行了初步细胞毒性试验。其中，化合物 1a、2a、5b-d、6b、7a、7c 和阿霉素的 IC 值低于 20µM，而其他化合物在高达 50µM 时活性较低或没有活性。引人注目的是，化合物 5c 对 HCT116 p53 结肠腺癌细胞、5e 对 CCRF-CEM 细胞和 MDA-MB-231-BCRP 乳腺癌细胞以及 6b 对 HCT116 p53 细胞和 HCT116 p53 细胞具有低于 1µM 的 IC 值的显著细胞毒性作用。
