PDF(Pubmed)
Abstract：
In this study, we designed two series of novel anthraquinone-based benzenesulfonamide derivatives and their analogues as potential carbonic anhydrase inhibitors (CAIs) and evaluated their inhibitory activities against off-target human carbonic anhydrase II (hCA II) isoform and tumor-associated human carbonic anhydrase IX (hCA IX) isoform. Most of these compounds exhibited good inhibitory activities against hCA II and IX. The compounds that exhibited the best hCA inhibition were further studied against the MDA-MB-231, MCF-7, and HepG2 cell lines under hypoxic and normoxic conditions. Additionally, the compounds exhibiting the best antitumor activity were subjected to apoptosis and mitochondrial membrane potential assays, which revealed a significant increase in the percentage of apoptotic cells and a notable decrease in cell viability. Molecular docking studies were performed to demonstrate the presence of numerous hydrogen bonds and hydrophobic interactions between the compounds and the active site of hCA. Absorption, distribution, metabolism, excretion (ADME) predictions showed that all of the compounds had good pharmacokinetic and physicochemical properties.
摘要：
在这项研究中,我们设计了两个系列新型蒽醌基苯磺酰胺衍生物及其类似物作为潜在的碳酸酐酶抑制剂(CAI),并评估了它们对脱靶人碳酸酐酶II(hCAII)亚型和肿瘤相关人碳酸酐酶IX(hCAIX)亚型的抑制活性.这些化合物中的大多数对hCAII和IX表现出良好的抑制活性。在低氧和常氧条件下针对MDA-MB-231、MCF-7和HepG2细胞系进一步研究了表现出最佳hCA抑制的化合物。此外,对表现出最佳抗肿瘤活性的化合物进行细胞凋亡和线粒体膜电位测定，这表明凋亡细胞的百分比显着增加，细胞活力显着降低。进行分子对接研究以证明化合物与hCA的活性位点之间存在许多氢键和疏水相互作用。吸收,分布，新陈代谢，排泄（ADME）预测表明，所有化合物均具有良好的药代动力学和理化性质。
