Theoretical study of ibotenic acid analogues, acting on exitatory amino acid receptors

G.M.CIUFFO; A.M.RODRIGUEZ; ENRIZ R D; E.A.JAUREGUI

Journal of the Argentine Chemical Society

ASOCIACIÓN QUÍMICA ARGENTINA

Lugar: Buenos Aires; Año: 1991 vol. 79 p. 161 - 172

0365-0375

lt is generally accepted that the carboxylic amino acidsL-glutamic acid and L-asparti c acid play a rol e as excitatory neurotransmittersat the central nervous system. ln the searchfor a structure-activityrelationship, we have made a theoretical conformational and electroniranalysis using nwlecular mechanics and semi-empírica/ MNDO calculationson compounds active on AMP A-receptors and NMDA-receptors.Severa/ molecules derivedfrom ibotenic acid are studied. Such molecu/es show a wide range of biological activities, some of themare NMDAreceptorsand the others are active on NMDA-receptors. The conformationaland electronic differences are analysed.We propose thatfolded conformations are active on AMPA-receptors,wereas extended conformations are active 011 NMDA-receptors. Withrespect to the net atomic charge, a difference on the amino groups ofactive molecules, on the two different receptors sites isfound.