Authors Manzoor, S; Prajapati, SK; Majumdar, S; Raza, MK; Gabr, MT; Kumar, S; Pal, K; Rashid, H; Kumar, S; Krishnamurthy, S; Hoda, N in ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER published article about in [Manzoor, Shoaib; Pal, Kavita; Rashid, Haroon; Hoda, Nasimul] Jamia Millia Islamia, Drug Design & Synth Lab, Dept Chem, New Delhi 110025, India; [Prajapati, Santosh Kumar; Majumdar, Shreyasi; Krishnamurthy, Sairam] Banaras Hindu Univ, Dept Pharmaceut Engn & Technol, Neurotherapeut Lab, Indian Inst Technol, Varanasi 221005, Uttar Pradesh, India; [Raza, Md Kausar] Indian Inst Sci, Dept Inorgan & Phys Chem, Bangalore 560012, Karnataka, India; [Gabr, Moustafa T.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA; [Kumar, Shivani; Kumar, Suresh] Guru Gobind Singh Indraprastha Univ Dwarka, Univ Sch Biotechnol, Sect 16C, New Delhi 110078, India in 2021, Cited 77. Category: indole-building-block. The Name is 4-Methoxybenzaldehyde. Through research, I have a further understanding and discovery of 123-11-5
Alzheimer’s disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by (HNMR)-H-1, (CNMR)-C-13, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC50 = 47.33 +/- 0.02 nM and 51.36 +/- 0.04 nM and moderate inhibition against BuChE; IC50 = 159.43 +/- 0.72 nM and 153.3 +/- 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced A beta(1- 42) aggregation in thioflavin T-assay at 10 mu M and 20 mu M, but BS-10 at 10 mu M and 20 mu M concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced A beta(1- 42) aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and A beta disaggregator for the treatment of AD. (C) 2021 Elsevier Masson SAS. All rights reserved.
Category: indole-building-block. About 4-Methoxybenzaldehyde, If you have any questions, you can contact Manzoor, S; Prajapati, SK; Majumdar, S; Raza, MK; Gabr, MT; Kumar, S; Pal, K; Rashid, H; Kumar, S; Krishnamurthy, S; Hoda, N or concate me.
Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles