Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
Department of Chemistry, Hazara University, Mansehra 21300, Pakistan.
Bioorg Chem. 2019 Aug;89:102999. doi: 10.1016/j.bioorg.2019.102999. Epub 2019 May 21.
Isoquinoline analogues (KA-1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11, all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as H NMR, C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1-9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12, 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues.
已合成了异喹啉类似物（KA-1 至 16），并对其对大肠杆菌胸苷磷酸化酶的抑制活性进行了评估。除化合物 11 外，与标准药物 7-脱氮黄嘌呤（IC=38.68±4.42µM）相比，所有其他类似物均表现出出色的胸苷抑制潜力，范围在 4.40±0.20 至 69.30±1.80µM 之间。已为所有化合物建立了构效关系，主要基于苯环上的取代模式。所有类似物均通过各种光谱技术（如 1H NMR、13C NMR 和 EI-MS）进行了表征。对异喹啉类似物与 TP 酶活性位点的结合相互作用进行了分子对接研究。此外，还基于不同浓度下的百分比抑制，在标准药物地塞米松存在的情况下，确定了异喹啉类似物（KA-1-9、14、12 和 16）的血管生成抑制潜力。在合成的类似物中，类似物 KA-12、14 和 16 表现出最强的血管生成抑制潜力。
