Synthesis, biological assessment and molecular modeling of new dihydroquinoline-3-carboxamides and dihydroquinoline-3-carbohydrazide derivatives as cholinesterase inhibitors, and Ca channel antagonists

Eur J Med Chem. 2011 Jan;46(1):1-10. doi: 10.1016/j.ejmech.2010.08.054. Epub 2010 Dec 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / chemical synthesis
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / chemistry
  • Calcium Channels / metabolism*
  • Catalytic Domain
  • Cattle
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterases / chemistry
  • Cholinesterases / metabolism*
  • Drug Design
  • Electrophorus
  • Hydrazines / chemical synthesis*
  • Hydrazines / chemistry
  • Hydrazines / pharmacology*
  • Models, Molecular*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Cholinesterase Inhibitors
  • Hydrazines
  • Quinolines
  • Cholinesterases
  • carbohydrazide