Al-Oudat Buthina A, Al-Shar'i Nizar A, Al-Balas Qosay A, Audat Suaad A, Alqudah Mohammad A Y, Hamzah Ali H, Hallak Ramez W, Bedi Mel, Bryant-Friedrich Amanda
Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Bioorg Chem. 2022 Mar;120:105657. doi: 10.1016/j.bioorg.2022.105657. Epub 2022 Feb 5.
In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I enzyme with IC of 1.28 ± 0.12 μM. Herein, lead optimization of this compound was achieved through targeting the central zinc atom and hydrophilic amino acid residues in the active site of the enzyme. Among the synthesized compounds, compound TS010 showed the most potent inhibitory activity with IC of 0.57 ± 0.04 μM. Compound TS013 also showed comparable activity to that of the lead compound with IC of 1.14 ± 0.03 μM. Molecular docking studies disclosed the binding mode of the compounds inside the active side of GLO-I enzyme.
在之前的一份报告中，我们描述了（E）-5-（（8-羟基喹啉-5-基）重氮基）-2-甲基苯磺酰胺作为GLO-I酶的有效抑制剂的发现，其IC50为1.28±0.12μM。在此，通过靶向该酶活性位点的中心锌原子和亲水氨基酸残基，实现了该化合物的先导优化。在合成的化合物中，化合物TS010表现出最有效的抑制活性，IC50为0.57±0.04μM。化合物TS013也表现出与先导化合物相当的活性，IC50为1.14±0.03μM。分子对接研究揭示了这些化合物在GLO-I酶活性位点内的结合模式。
