N-SALICYLOYL AMIDES AND THEIR SALTS: SYNTHESIS, BIOLOGICAL ACTIVITY AND TOXICITY

Abstract

The Schotten-Baumann reaction was used to synthesize N-salicyloyl derivatives of Morpholine, Glycine and gamma-aminobutyric acid in the process between salicyloyl chloride with morpholine, glycine or gamma-aminobutyric acid with high yield. Sodium and lithium salts of the salicylamides were synthesized by the reaction of an amide with sodium ethylate or lithium hydroxide in inert solvent. The synthesized compounds were charachterized by 1H nuclear magnetic resonance spectra and elemental analysis. Purity was checked by thin layer chromatography. Quantitative analysis of metal ions was done by potentiometry. To select the most promising compounds exhibiting psychotropic (Pa > 0.8) and antiviral (Pa about 0.5) activities, computer analysis was carried out through the PASS program. In the present study, psychotropic (the open-field exploratory test, the forced swim test, the elevated plus-maze test, the passive avoidance test), analgesic (current vocalization threshold) activities and acute toxicity were evaluated. The results of psychotropic activity revealed that amides possess significant psychotropic activity and low acute toxicity. Disodium salicylurate showed a significant antiamnesic action. The results suggested a significant antidepressant activity and antiamnesic action for dilithium salicylurate and sodium salt of salycyloyl morphlide, a psychostimulant action for lithium salt of salicyloyl morphlide. Lithium gamma-(N-salycylamino)butyrate demonstrated psychostimulant and antiamnesic activities. Our present investigation demonstrated that all compounds are very safe for consumption with high LD50 value. All obtained compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex viruses 1 and 2, vaccinia virus, vesicular stomatitis virus, HIV-1 and HIV-2. These compounds were evaluated against human cervix carcinoma cells (HeLa) and CEM T-lymphocytes as well as murine leukemia cells (L1210). The antiviral activity studies depicted that none of the tested compounds were active against DNA or RNA viruses.