Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, European University of Lefke, Northern Cyprus, Turkey.
Chem Biol Drug Des. 2021 Aug;98(2):270-282. doi: 10.1111/cbdd.13896. Epub 2021 Jun 12.
The purpose of this study was to synthesize imidazo[2,1-b]thiazole derivatives, characterize them with spectroscopical techniques and investigate for cytotoxic and apoptotic effects on glioma C6 cancer cell line. The in vitro anticancer activities were also investigated against focal adhesion kinase. Most of the compounds, particularly the derivatives carrying 3-oxo-1-tiya-4-azaspiro[4.5]decane moiety, exhibited higher or comparable activities in comparison with the reference drug, cisplatin. Compounds with methyl, propyl, phenyl moieties at the eighth and second position of the spirothiazolidinone ring showed high FAK inhibitory activities. In addition, molecular docking studies shed light on the binding modes of the synthesized compounds. The critical interactions with amino acid residues located in the active site were revealed. The results obtained from both biological assay data and computational results might provide insight into developing new inhibitors against focal adhesion kinase.
本研究旨在合成咪唑并[2,1-b]噻唑衍生物，用光谱技术对其进行表征，并研究其对神经胶质瘤 C6 癌细胞系的细胞毒性和凋亡作用。还研究了它们对粘着斑激酶的体外抗癌活性。大多数化合物，特别是带有 3-氧代-1-硫杂-4-氮杂螺[4.5]癸烷部分的衍生物，表现出比参考药物顺铂更高或相当的活性。在螺噻唑烷酮环的第八位和第二位带有甲基、丙基、苯基部分的化合物表现出高的粘着斑激酶抑制活性。此外，分子对接研究揭示了合成化合物的结合模式。揭示了与位于活性部位的氨基酸残基的关键相互作用。从生物测定数据和计算结果中获得的结果可能为开发针对粘着斑激酶的新型抑制剂提供思路。
