Study of Capah Membranetropic Action on the Artificial Biomembranes

Abstract

The drugs neurotropic effects are known to be connected with their ability to change the physicochemical parameters of membrane organisation. Having been investigated last time, phosphorylacetic acid hydrazides R(R')P(O)CH₂C(O)NHNH₂ display neuroprotective, memory enhancing and antidepressive acttvities. The lead representative of these series is CAPAH (I)(R=Me₂,NC₆H₄; R'=CIC₂H₄O) We have now studied these compounds influence on the organization of model phospholipid membranes from egg yolk phosphatidilcholine (PC) ³¹P NMR technique was applied as particularly useful analytical tool for he study of the polymorphic phase behavior of hydrated phospholipids. The main feature of the CAPAH effect on ³¹P NMR spectra consists of an appearance of narrow symmetrical signal indicatingeffectively isotropic motion of the phospholipid molecules. PHOSENAZID (II) (R=R'=C₆H₅) renders the similar action on the membranes. It is confirmed by earlier obtamed Infrared spectroscopy data that showed the formation of intermolecular hydrogen bond between carbonyl groupof phospholipid molecule and hydrazide fragment of CAPAH^|2|. N-acyl derivative of CAPAH (III) did not affect the PC liposomes. Using of CAPAH and PHOSENAZID hydrochloride salts (IV.V) causes more drastic changes in the bilayer structure of liposomes apparently in the consequence of the additional interaction of salt anion with positive charged PC choline fragment. The results obtained are inan agreement with the preliminary studies of antioxidant effect of these compounds in vitro. Thus, the hydrochloride salts (IV, V) possess more marked influence on lipid peroxidation process in membranes of rat brain, and all tested hydrazides form the line increasing antioxidant activity (III)→ (11)→ (I)=(V)→ (Vl).