Unknown

Dataset Information

0

Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT4 receptors activities for the treatment of Alzheimer's disease.

ABSTRACT: A rigidification strategy was applied to the preclinical candidate donecopride, an acetylcholinesterase inhibitor possessing 5-HT4R agonist activity. Inspired by promising bioactive benzisoxazole compounds, we have conducted a pharmacomodulation study to generate a novel series of multitarget directed ligands. The chemical synthesis of the ligand was optimized and compounds were evaluated in vitro against each target and in cellulo. Structure-activity relationship was supported by docking analysis in human acetylcholinesterase binding site. Among the synthesized compounds, we have identified a novel hybrid 32a (3-[2-[1-(cyclohexylmethyl)-4-piperidyl]ethyl]-4-methoxy-1,2-benzoxazole) able to display nanomolar acetylcholinesterase inhibitory effects and nanomolar Ki for 5-HT4R.

SUBMITTER: Lalut J 

PROVIDER: S-EPMC7033111 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT<sub>4</sub> receptors activities for the treatment of Alzheimer's disease.

Lalut Julien J   Payan Hugo H   Davis Audrey A   Lecoutey Cédric C   Legay Rémi R   Sopkova-de Oliveira Santos Jana J   Claeysen Sylvie S   Dallemagne Patrick P   Rochais Christophe C  

Scientific reports 20200220 1

A rigidification strategy was applied to the preclinical candidate donecopride, an acetylcholinesterase inhibitor possessing 5-HT<sub>4</sub>R agonist activity. Inspired by promising bioactive benzisoxazole compounds, we have conducted a pharmacomodulation study to generate a novel series of multitarget directed ligands. The chemical synthesis of the ligand was optimized and compounds were evaluated in vitro against each target and in cellulo. Structure-activity relationship was supported by doc  ...[more]

Similar Datasets

Unknown Acetylcholinesterase and butyrylcholinesterase inhibitory activities of khellactone coumarin derivatives isolated from Peucedanum japonicum Thurnberg.
| S-EPMC7730441 | biostudies-literature
Unknown Design of Curcumin and Flavonoid Derivatives with Acetylcholinesterase and Beta-Secretase Inhibitory Activities Using in Silico Approaches.
| S-EPMC7464027 | biostudies-literature
Unknown Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii.
| S-EPMC8260592 | biostudies-literature
Unknown Polyketide Derivatives from the Endophytic Fungus Phaeosphaeria sp. LF5 Isolated from Huperzia serrata and Their Acetylcholinesterase Inhibitory Activities.
| S-EPMC8955197 | biostudies-literature
Unknown Acetylcholinesterase Inhibitory Activities of Essential Oils from Vietnamese Traditional Medicinal Plants.
| S-EPMC9610647 | biostudies-literature
Unknown Urease inhibitory activities of ?-boswellic acid derivatives.
| S-EPMC3575251 | biostudies-literature
Unknown Synthesis of some phenylpropanoid glycosides (PPGs) and their acetylcholinesterase/xanthine oxidase inhibitory activities.
| S-EPMC6263338 | biostudies-literature
Unknown Synthesis and Evaluation of the Acetylcholinesterase Inhibitory Activities of Some Flavonoids Derived from Naringenin.
| S-EPMC8651387 | biostudies-literature
Unknown Molecular interaction of human acetylcholinesterase with trans-tephrostachin and derivatives for Alzheimer's disease.
| S-EPMC7501440 | biostudies-literature
Unknown 3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer's disease, with acetylcholinesterase and monoamine oxidase inhibitory properties.
| S-EPMC4904743 | biostudies-literature