Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Int J Biol Macromol. 2021 Feb 15;170:1-12. doi: 10.1016/j.ijbiomac.2020.12.121. Epub 2020 Dec 19.
In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K values in the range of 19.28-135.88 nM for α-glycosidase (K value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (K value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (K value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (K value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (K value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.
在这项研究中，合成了新型喹唑啉酮衍生物 7a-n，并对包括α-糖苷酶、乙酰胆碱酯酶、丁酰胆碱酯酶、人碳酸酐酶 I 和 II 在内的代谢酶进行了评估。与使用的标准抑制剂相比，这些化合物表现出高抑制活性，α-糖苷酶的 K 值范围为 19.28-135.88 nM（标准抑制剂的 K 值为 187.71 nM），乙酰胆碱酯酶的 K 值范围为 0.68-23.01 nM（标准抑制剂的 K 值为 53.31 nM），丁酰胆碱酯酶的 K 值范围为 1.01-29.56 nM（标准抑制剂的 K 值为 58.16 nM），人碳酸酐酶 I 的 K 值范围为 10.25-126.05 nM（标准抑制剂的 K 值为 248.18 nM），人碳酸酐酶 II 的 K 值范围为 13.46-178.35 nM（标准抑制剂的 K 值为 323.72 nM）。此外，选择了对每种酶最有效的化合物，以评估这些化合物在靶酶活性部位的相互作用模式。标题化合物 7a-n 对 MCF-7 和 LNCaP 癌细胞系的细胞毒性试验表明，这些化合物没有显示出显著的细胞毒性作用。
