95767-60-5Relevant articles and documents
Acetamide Derivatives of Chromen-2-ones as Potent Cholinesterase Inhibitors
Prasad, Suchita,Kumar, Bipul,Kumar, Shiv,Chand, Karam,Kamble, Shashank S.,Gautam, Hemant K.,Sharma, Sunil K.
, (2017/08/07)
Alzheimer's disease (AD), a neurodegenerative disorder, is a serious medical issue worldwide with drastic social consequences. Inhibition of cholinesterase is one of the rational and effective approaches to retard the symptoms of AD and, hence, consistent efforts are being made to develop efficient anti-cholinesterase agents. In pursuit of this, a series of 19 acetamide derivatives of chromen-2-ones were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential. All the synthesized compounds exhibited significant anti-AChE and anti-BChE activity, with IC50 values in the range of 0.24–10.19 μM and 0.64–30.08 μM, respectively, using donepezil hydrochloride as the standard. Out of 19 compounds screened, 3 compounds, viz. 22, 40, and 43, caused 50% inhibition of AChE at 0.24, 0.25, and 0.25 μM, respectively. A kinetic study revealed them to be mixed-type inhibitors, binding with both the CAS and PAS sites of AChE. The above-selected compounds were found to be effective inhibitors of AChE-induced and self-mediated Aβ1–42 aggregation. ADMET predictions demonstrated that these compounds may possess suitable blood–brain barrier (BBB) permeability. Hemolytic assay results revealed that these compounds did not lyse human RBCs up to a thousand times of their IC50 value. MTT assays performed for the shortlisted compounds showed them to be negligibly toxic after 24 h of treatment with the SH-SY5Y neuroblastoma cells. These results provide insights for further optimization of the scaffolds for designing the next generation of compounds as lead cholinesterase inhibitors.
Synthesis and optimization of peptidomimetics as HIV entry inhibitors against the receptor protein CD4 using STD NMR and ligand docking
Neffe, Axel T.,Bilang, Matthias,Meyer, Bernd
, p. 3259 - 3267 (2008/03/14)
We recently described the design and synthesis of a novel CD4 binding peptidomimetic as a potential HIV entry inhibitor with a KD value of ～35 M and a high proteolytic stability [A. T. Neffe and B. Meyer, Angew. Chem., Int. Ed., 2004, 43, 2937-2940]. Based on saturation transfer difference (STD) NMR analyses and docking studies of peptidomimetics we now report the rational design, synthesis, and binding properties of 11 compounds with improved binding affinity. Surface plasmon resonance (SPR) resulted in a KD = 10 M for the best peptidomimetic XI, whose binding affinity is confirmed by STD NMR (KD = 9 M). The STD NMR determined binding epitope of the ligand indicates a very similar binding mode as that of the lead structure. The binding studies provide structure activity relationships and demonstrate the utility of this approach. The Royal Society of Chemistry 2006.
