Browsing by Author "Mahmoud W.R."

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    Neurobehavioral investigation and acetylcholinesterase inhibitory activity study for some new coumarin derivatives
    (Elsevier Masson SAS, 2019) Mahmoud W.R.; Nissan Y.M.; Elsawah M.M.; Refaey R.H.; Ragab M.F.; Amin K.M.; Pharmaceutical Chemistry Department; Faculty of Pharmacy; Cairo University; Kasr Elini St; Cairo; 11562; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Giza; Egypt; Drug Research Center; Cairo; Egypt; Pharmacology and Toxicology Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Giza; Egypt
    Twenty four 6-aminocoumarin based derivatives were synthesized according to two schemes. All the compounds were screened for their acetylcholinesterase inhibitory activity where compound 5b proved to be the most potent AChE inhibitor with (IC50 = 37 nM) compared to tacrine and donepezil (IC50 = 55.0 and 59.0 nM, respectively). Six compounds 2f, 2g, 4b, 5b, 8b and 9b revealed superior activity over donepezil and a conclusive structure activity relationship study was conducted explaining the obtained results. Furthermore, compounds 2f, 4b and 5b were investigated for their neurobehavioral effect in vivo. All the tested compounds showed improvement of neurobehavioral experiments using donepezil as reference drug. In addition, compounds 2f, 4b and 5b were able to reduce extracellular deposition of amyloid beta 42 in a comparable manner to donepezil. The binding modes of the synthesized compounds were evaluated in silico via molecular docking in the active site of AChE, as well as molecular dynamics simulation study. A pharmacophore model was generated for the newly synthesized compounds. � 2019 Elsevier Masson SAS