基于杂环的查尔酮衍生物作为抗增殖剂的合成与评价
Synthesis and Evaluation of Heterocycles Based Chalcone Derivatives as Antiproliferative Agents.
作者信息
Çavuşoğlu Betül Kaya, Atlı Özlem, Görmüş Gözde, Özkay Yusuf, Kaplancıklı Zafer Asım
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
出版信息
Anticancer Agents Med Chem. 2018;18(7):1044-1053. doi: 10.2174/1871520618666180105163657.
BACKGROUND
The lack of selectivity and development of drug-resistance encourage researchers to search for novel, more efficient and multi-targeted agents with less toxicity.
OBJECTIVE
In this paper, a series of novel chalcone derivatives bearing diverse heterocycles have been synthesized and evaluated for their antiproliferative activity against A549 (Human Lung Adenocarcinoma) and C6 (Rat Brain Glioma) cells.
METHOD
Structures of the title compounds (3-18) were verified by FT-IR, 1H NMR, 13C NMR, HRMS spectral data and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis.
RESULTS
Compounds 9 and 15 were revealed as the most promising cytotoxic agents due to their selectivity towards A549 cells with lower IC50 values (IC50=0.05 µM and IC50=0.0316 µM) than cisplatin (IC50=0.06 µM). Flow cytometric analysis of compounds 9 and 15 showed that they affected lung cancer cells by the apoptotic pathway.
CONCLUSION
It is concluded that this study will contribute to the research of novel antiproliferative agents.
背景
缺乏选择性以及耐药性的产生促使研究人员寻找新型、更高效且多靶点的低毒药物。
目的
本文合成了一系列带有不同杂环的新型查尔酮衍生物，并评估了它们对A549（人肺腺癌）和C6（大鼠脑胶质瘤）细胞的抗增殖活性。
方法
通过傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）、高分辨质谱（HRMS）光谱数据和元素分析对标题化合物（3-18）的结构进行了验证。使用MTT法、BrdU法和流式细胞术分析评估了化合物的抗增殖活性。
结果
化合物9和15被证明是最有前景的细胞毒性药物，因为它们对A549细胞具有选择性，其半数抑制浓度（IC50）值（IC50 = 0.05 μM和IC50 = 0.0316 μM）低于顺铂（IC50 = 0.06 μM）。对化合物9和15的流式细胞术分析表明，它们通过凋亡途径影响肺癌细胞。
结论
得出的结论是，本研究将有助于新型抗增殖药物的研究。
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