| Title : Synthesis, biological evaluation and modeling of hybrids from tetrahydro-1H-pyrazolo[3,4-b]quinolines as dual cholinestrase and COX-2 inhibitors - Mroueh_2020_Bioorg.Chem_100_103895 |
| Author(s) : Mroueh M , Faour WH , Shebaby WN , Daher CF , Ibrahim TM , Ragab HM |
| Ref : Bioorg Chem , 100 :103895 , 2020 |
|
Abstract :
New tetrahydro-1H-pyrazolo[3,4-b]quinoline derivatives were designed, synthesized and characterized as dual anticholinestrase and cyclooxygenase-2 inhibitors. The in vitro and in vivo anti-cholinesterase evaluation exhibited promising activities with lower hepatotoxicity for many candidates compared to tacrine as a reference. Furthermore, their anti-inflammatory activity using in vitro (COX-1/COX-2) inhibitory assay demonstrated superior activity to celecoxib with higher selectivity indices for some compounds. In addition, some candidates showed extended anti-inflammatory activity by inhibiting COX-2 protein induction. Besides, in silico docking experiments of the active compounds against hAChE rationalized the observed in vitro AChE inhibitory activity. In conclusion, this work provides an extension of the chemical space of tetrahydro-1H-pyrazolo[3,4-b]quinoline chemotype for the anticholinestrase and anti-inflammatory activity. This would aid to minimize the possible neuroinflammation linked to the pathogenesis of Alzheimer's disease. |
| PubMedSearch : Mroueh_2020_Bioorg.Chem_100_103895 |
| PubMedID: 32413626 |
Mroueh M, Faour WH, Shebaby WN, Daher CF, Ibrahim TM, Ragab HM (2020)
Synthesis, biological evaluation and modeling of hybrids from tetrahydro-1H-pyrazolo[3,4-b]quinolines as dual cholinestrase and COX-2 inhibitors
Bioorg Chem
100 :103895
Mroueh M, Faour WH, Shebaby WN, Daher CF, Ibrahim TM, Ragab HM (2020)
Bioorg Chem
100 :103895