Abstract
A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a “one pot” condensation reaction to α-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-α and IL-1β production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity.
Graphical Abstract
[The pharmacological evaluation of eight N-phthaloyl amino acids 2a–h, including their anti-inflammatory and cytotoxic effects and nitric oxide, TNF-α, and IL-1β production, is described.]
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Acknowledgments
We would like to thank the Brazilian National Research Council (CNPq), FACEPE, and FIOCRUZ for financial support. MVOC received a CNPq doctoral scholarship and currently receives a FACEPE researcher scholarship. We also thank the Department of Fundamental Chemistry-UFPE for recording the 1H-NMR and IR spectra of all compounds.
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Leite, A.C.L., Barbosa, F.F., Cardoso, M.V.d. et al. Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes. Med Chem Res 23, 1701–1708 (2014). https://doi.org/10.1007/s00044-013-0730-1
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DOI: https://doi.org/10.1007/s00044-013-0730-1