Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstrasse 1, 8010 Graz, Austria.
Institute of Pharmaceutical Sciences, Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.
Molecules. 2018 Nov 7;23(11):2902. doi: 10.3390/molecules23112902.
The cytotoxic and antiprotozoal activities of the phytoquinoide, jacaranone, and related compounds have been an ongoing topic in recent drug discovery. Starting from the natural product-derived cyclohexadienone scaffold, a series of nitrogen-containing derivatives were synthesized and subsequently evaluated for their antiproliferative and antiprotozoal activity. Anticancer potency was analyzed using different types of cancer cell lines: MDA-MB-231 breast cancer, CCRF-CEM leukemia, HCT-116 colon cancer, U251 glioblastoma, and, in addition, non-tumorigenic MRC-5 lung fibroblasts. Antiproliferative activities at micromolar concentrations could be shown. Antiprotozoal activity was assessed against NF54 and STIB900. For all compounds, selectivity indices (SI) were calculated based on assessed cytotoxicity towards L6 cells. In addition, the structure-activity-relationships and physicochemical parameters of these compounds are discussed.
植物醌类化合物 Jacaranone 及其相关化合物的细胞毒性和抗原生动物活性一直是最近药物发现的一个热门话题。从天然产物衍生的环己二烯酮支架出发，合成了一系列含氮衍生物，并对其增殖抑制和抗原生动物活性进行了评价。采用不同类型的癌细胞系分析抗癌活性：MDA-MB-231 乳腺癌、CCRF-CEM 白血病、HCT-116 结肠癌、U251 神经胶质瘤，此外还有非致瘤性的 MRC-5 肺成纤维细胞。在微摩尔浓度下可以显示出抗增殖活性。抗原生动物活性针对 NF54 和 STIB900 进行评估。对于所有化合物，根据对 L6 细胞的细胞毒性评估计算了选择性指数 (SI)。此外，还讨论了这些化合物的结构-活性关系和物理化学参数。
