Physostigmine analogs anticholinesterases: effects of the lengthening of the N-carbamic chain on the inhibition kinetics

Biochim Biophys Acta. 1992 Apr 17;1120(3):262-6. doi: 10.1016/0167-4838(92)90246-a.

Abstract

Data are presented about the inhibitor power of new carbamates against acetylcholinesterase. The study was carried out on two series of physostigmine analogs, N-alkyl and N-methyl,N-alkylphysostigmines. For these inhibitors, the second-order rate constants for inhibition, ki, and the first-order rate constants of reactivation, k3, have been determined. From the reported results, electronic, hydrophobic and steric effects, due to the enhancement of the alkyl chain, may have influenced all kinetics parameters discussed. In comparison to physostigmine, both the new N-methyl,N-alkylphysostigmines and the N-alkylphysostigmines showed a non-linear decrease in the values of ki and k3. This study presents the hydrophobic interactions as an important factor not only in determining carbamylation but also decarbamylation rates constants.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carbamates / chemistry*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacokinetics
  • Cholinesterase Inhibitors / pharmacology*
  • Enzyme Activation / drug effects
  • Physostigmine / analogs & derivatives
  • Physostigmine / pharmacokinetics
  • Physostigmine / pharmacology*
  • Protein Conformation
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Physostigmine