Mohareb Rafat Milad, Abdelaziz Mahmoud A, Jame Rasha, Omer Noha, Labib Hanan Maged
Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt.
Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk, 71491, Kingdom of Saudi Arabia.
Anticancer Agents Med Chem. 2025;25(2):134-149. doi: 10.2174/0118715206323592240909101754.
The coumarin nuclei, which exist in many heterocyclic compounds, has gained a lot of attention over the past decade due to their wide range of biological activities such as antibacterial, anticoagulant, antiviral, antifungal, anticancer, and anti-inflammatory properties.
The multi-component reactions of 5,5-dimethylcyclohexane-1,3-dione with acetophenone derivatives and triethoxymethane produced biologically active target chromene molecules and their fused derivatives.
The reaction of 5,5-dimethylcyclohexane-1,3-dione and each of triethoxymethane and acetophenone derivatives 3a-g in absolute ethanol containing triethylamine gave the 4,6,7,8-tetrahydro-5H-chromen-5-one derivatives 4a-g. Compounds 4a-d were used for further heterocyclization reactions to produce biologically active fused pyrazole, thiophene, and thiazole derivative corporate with the chromenes caffold.
The cytotoxicity of the synthesized compounds were evaluated using six cancer cell lines together with c-Met kinase and PC-3 cell line inhibitions. In addition, cytotoxicity toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa was carried out as well as the in-vitro cytotoxic potential for all compounds against peripheral blood lymphocytes (PBL) extracted from healthy donors. Morphological changes of the A549 cell line by the two most active compounds were also studied.
The synthesized heterocyclic compounds were originally obtained from 5,5-dimethylcyclohexane- 1,3-dione. Several of the produced compounds exhibited high inhibitions toward several cancer cell lines proving high inhibitions, therefore, encouraging further studies to synthesize heterocyclic compounds based on chromene scaffold.
香豆素核存在于许多杂环化合物中，在过去十年中因其广泛的生物活性，如抗菌、抗凝、抗病毒、抗真菌、抗癌和抗炎特性而备受关注。
5,5 - 二甲基环己烷 - 1,3 - 二酮与苯乙酮衍生物和三乙氧基甲烷的多组分反应生成了具有生物活性的目标色烯分子及其稠合衍生物。
5,5 - 二甲基环己烷 - 1,3 - 二酮与三乙氧基甲烷和苯乙酮衍生物3a - g在含有三乙胺的无水乙醇中反应，得到4,6,7,8 - 四氢 - 5H - 色烯 - 5 - 酮衍生物4a - g。化合物4a - d用于进一步杂环化反应，以生成与色烯骨架结合的具有生物活性的稠合吡唑、噻吩和噻唑衍生物。
使用六种癌细胞系以及对c - Met激酶和PC - 3细胞系的抑制作用来评估合成化合物的细胞毒性。此外，还对肝细胞癌HepG2和宫颈癌HeLa进行了细胞毒性测试，以及所有化合物对从健康供体提取的外周血淋巴细胞（PBL）的体外细胞毒性潜力测试。还研究了两种活性最高的化合物对A549细胞系的形态学变化。
合成的杂环化合物最初由5,5 - 二甲基环己烷 - 1,3 - 二酮制得。所产生的几种化合物对几种癌细胞系表现出高度抑制作用，因此证明具有很高的抑制作用，这鼓励进一步研究基于色烯骨架合成杂环化合物。
