Jain Priti, Wadhwa Pankaj K, Gunapati Sinduri, Jadhav Hemant R
Computational Laboratory, Medicinal Chemistry Division, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333 031, India; Medicinal Chemistry Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333 031, India.
Medicinal Chemistry Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333 031, India.
Bioorg Med Chem. 2016 Jun 1;24(11):2567-2575. doi: 10.1016/j.bmc.2016.04.023. Epub 2016 Apr 12.
The identification of a series of sulfonyl-amino-acetamides as BACE-1 (β-secretase) inhibitors for the treatment of Alzheimer's disease is reported. The derivatives were designed based on the docking simulation study, synthesized and assessed for BACE-1 inhibition in vitro. The designed ligands revealed desired binding interactions with the catalytic aspartate dyad and occupance of S1 and S2' active site regions. These in silico results correlated well with in vitro activity. Out of 33 compounds synthesized, 12 compounds showed significant inhibition at 10μM concentration. The most active compound 2.17S had IC50 of 7.90μM against BACE-1, which was concomitant with results of in silico docking study.
报道了一系列磺酰基氨基乙酰胺作为治疗阿尔茨海默病的β-分泌酶1（BACE-1）抑制剂的鉴定。这些衍生物基于对接模拟研究进行设计，合成后并在体外评估其对BACE-1的抑制作用。设计的配体显示出与催化天冬氨酸二联体的预期结合相互作用以及对S1和S2'活性位点区域的占据。这些计算机模拟结果与体外活性良好相关。在合成的33种化合物中，有12种化合物在10μM浓度下表现出显著抑制作用。活性最高的化合物2.17S对BACE-1的IC50为7.90μM，这与计算机模拟对接研究的结果一致。
