Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
Bioorg Chem. 2019 Oct;91:103137. doi: 10.1016/j.bioorg.2019.103137. Epub 2019 Jul 23.
Design, synthesis and characterization of new trinary Benzocoumarin-Thiazoles-Azomethine derivatives having three bioactive scaffolds in a single structural unit were carried out. The newly synthesized molecules were investigated for the inhibitory activity on human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP) isozymes. All the tested compounds exhibited the potent inhibition profile on both isozymes of alkaline phosphatase i.e., h-TNAP and h-IAP. Molecular docking studies were performed to explore the putative binding mode of interactions of selective inhibitors. Moreover, the synthesized derivatives were evaluated against cervical cancer cell line, HeLa and a few compounds exhibited significant inhibition in the range of 21.0-69.7%. The derivatives can be potential and selective alkaline phosphatase inhibitors for future studies.
设计、合成并表征了新型三元苯并香豆素-噻唑-亚甲胺衍生物,它们在一个单一的结构单元中具有三个生物活性支架。研究了新合成的分子对人组织非特异性碱性磷酸酶(h-TNAP)和人肠道碱性磷酸酶(h-IAP)同工酶的抑制活性。所有测试的化合物对碱性磷酸酶同工酶 h-TNAP 和 h-IAP 都表现出很强的抑制作用。进行了分子对接研究,以探索选择性抑制剂相互作用的可能结合模式。此外,还对合成的衍生物进行了抗宫颈癌细胞系 HeLa 的活性评价,部分化合物的抑制活性在 21.0-69.7%范围内。这些衍生物可能是未来研究中潜在的、选择性的碱性磷酸酶抑制剂。