Shaik, Jeelan Basha published the artcileSynthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents, Quality Control of 15029-36-4, the publication is European Journal of Medicinal Chemistry (2016), 219-232, database is CAplus and MEDLINE.
A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties was developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC50 values ranging from 0.003 to 0.357 μM which is 2-220 folds more potent than the pos. control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC50 7.98-15.99 μM). Specifically, the most potent AChE inhibitor, I (NR1R2 = NHCH2C6H4Br-3) (II), (IC50 0.003 ± 0.0007 μM) has an excellent antioxidant profile as determined by the ABTS method (IC50 7.98 ± 0.77 μM). Moreover, cell viability studies in SK N SH cells showed that the compounds I (NR1R2 = NHCH2C6H4Br-2, NHCH2C6H4Br-3, NHCH2C6H4Cl-2, NHCH2C6H4Cl-3, NHCH2C6H4CMe3-4) (III) have significant neuroprotective effects against H2O2-induced cell death, and are not neurotoxic at all concentrations except I (NR1R2 = NHCH2C6H4CMe3-4) and II. The kinetic anal. of compound II proved that it is a mixed-type inhibitor for EeAChE (Ki1 0.0103 μM and Ki2 0.0193 μM). Accordingly, the mol. modeling study demonstrated that III with a substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of Aβ induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor II is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapeutic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents.
European Journal of Medicinal Chemistry published new progress about 15029-36-4. 15029-36-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Aliphatic hydrocarbon chain,Amide, name is 2-Cyano-N-ethylacetamide, and the molecular formula is C4H6O3, Quality Control of 15029-36-4.
Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics