| Title : Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multi-target Ligands Directed towards Relevant Alzheimer's Targets - Purgatorio_2020_ChemMedChem_15_1947 |
| Author(s) : Purgatorio R , Kulikova L , Pisani L , Catto M , de Candia M , Carrieri A , Cellamare S , De Palma A , Beloglazkin A , Raesi GR , Voskressensky L , Altomare CD |
| Ref : ChemMedChem , 15 :1947 , 2020 |
|
Abstract :
A number of 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-one derivatives were synthesized and screened against different targets involved in Alzheimer's Disease (AD) onset and progression, such as acetyl- and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of beta-amyloid (Abeta) and reactive oxygen species (ROS) production. Thus, compounds showing multifaceted profiles of promising anti-AD features were identified as derivatives 1c, 3b, 4 and 5a, returning well-balanced multi-targeting inhibitory activities. Moreover, compound 1f, a potent and selective human MAO B inhibitor (IC50 = 0.89 muM), proved to be a safe neuroprotectant in human neuroblastoma cell line (SH-SY5Y) by improving viability impaired by Abeta1-42 and pro-oxidant insult. Furthermore, structure-activity relationships (SARs) and docking models were derived in order to assist further hit-to-lead optimization stage. |
| PubMedSearch : Purgatorio_2020_ChemMedChem_15_1947 |
| PubMedID: 32716595 |
Purgatorio R, Kulikova L, Pisani L, Catto M, de Candia M, Carrieri A, Cellamare S, De Palma A, Beloglazkin A, Raesi GR, Voskressensky L, Altomare CD (2020)
Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multi-target Ligands Directed towards Relevant Alzheimer's Targets
ChemMedChem
15 :1947
Purgatorio R, Kulikova L, Pisani L, Catto M, de Candia M, Carrieri A, Cellamare S, De Palma A, Beloglazkin A, Raesi GR, Voskressensky L, Altomare CD (2020)
ChemMedChem
15 :1947