Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes

A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a "one pot" condensation reaction to alpha-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide. Most of the compounds effectively suppressed nitric oxide production in murine cells stimulated with lipopolysaccharide. N-phthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-alpha and IL-1 beta production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity.