Synthesis, biological assessment and molecular modeling of new dihydroquinoline-3-carboxamides and dihydroquinoline-3-carbohydrazide derivatives as cholinesterase inhibitors, and Ca channel antagonists.
The synthesis, biological evaluation, and molecular modeling of new 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides(4), 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide (6), and some hexahydropyrimido[5,4-c]quinoline-2,5-diones (9) produced earlier by our laboratory, as AChE/BuChE inhibitors, is described. From these analyses compound 4c resulted equipotent regarding the inhibition of cholinesterases'; inhibitors 6k, 9a, 9b were selective for AChE, whereas product 4d proved selective for BuChE. Docking analysis has been carry out in order to identify the binding mode in the active site, and to explain the observed selectivities. Only compound 9a has been shown to decrease K(+)-induced calcium signals in bovine chromaffin cells.
Laboratoire de Chimie Thérapeutique Equipe 2SBP EA4267, 4 place saint Jacques 25030 Besancon Cedex, France. isabelle.tomassoli@edu.univ-fcomte.fr
Isabelle
I
Tomassoli
Lhassane
L
Ismaili
Marc
M
Pudlo
Cristóbal
C
de Los Ríos
Elena
E
Soriano
Inés
I
Colmena
Luis
L
Gandía
Luis
L
Rivas
Abdelouahid
A
Samadi
José
J
Marco-Contelles
Bernard
B
Refouvelet
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002802:Cholinesterases / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004593:Electrophorus; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002800:Cholinesterase Inhibitors; D006834:Hydrazines; D011804:Quinolines; D002802:Cholinesterases; C019289:carbohydrazide