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Synthesis, computational evaluation and pharmacological assessment of acetylsalicylic esters as anti-inflammatory agents

  • Raffaella Mancuso
  • Nadia Ferlazzo
  • Giorgio De Luca
  • Roberta Amuso
  • Antonio Palumbo Piccionello
  • Salvatore V. Giofrè
  • Michele Navarra
  • Bartolo Gabriele
Original Research
  • 37 Downloads

Abstract

A convenient approach to the synthesis of alkyl esters of aspirin (ASA-OR) has been developed. The synthesis of ASA-OR has been realized in two steps: (1) direct esterification of salicylic acid with alcohols in the presence of dicyclohexylcarbodiimide to give alkyl salicylates (SAL-OR); (2) acetylation of SAL-OR with acetyl chloride to yield ASA-OR. Molecular mechanics simulations, performed to calculate the kinetic radii of several ASA-OR, indicated that the pentyl and hexyl acetylsalicylates possess the best properties to cross cell membranes. The in vitro biological tests demonstrate their anti-inflammatory activity, superimposable to that of aspirin. The results of our study suggest that ASA-OR may be used as anti-inflammatory drugs for topical application.

Keywords

Acetylsalicylic acid Acetylsalicylic esters Anti-inflammatory activity Aspirin Computational study 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2284_MOESM1_ESM.docx (1007 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical TechnologiesUniversity of CalabriaRendeItaly
  2. 2.Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
  3. 3.Institute on Membrane TechnologyNational Research Council (ITM-CNR)RendeItaly
  4. 4.Department of Biological, Chemical and Pharmaceutical Science and Technology-STEBICEFUniversity of PalermoPalermoItaly

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