Anti-inflammatory activity of polyamide dendrimers bearing bile acid termini synthesized via SPAAC

  • Ana M. Garzón-Porras
  • Diego L. Bertuzzi
  • Kurt Lucas
  • Catia OrnelasEmail author
Research Paper


Inflammation is a general pathomechanism associated with numerous diseases of global impact such as many cancers, metabolic disorders, and neurodegenerative and autoimmune diseases. The development of drugs that can treat chronic inflammation, in an effective way and that are well tolerated by the patients, is an active research area that pursues the treatment for hundreds of diseases. Dendrimers recently appeared as a convenient starting point for the design of anti-inflammatory drugs due to its nanosize, well-defined branched structure, multivalency, and versatility. In this work, polyamide dendrimers with 1 ➔ 3 connectivity were synthesized and functionalized with three types of bile acids (BAs): cholic acid (CA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). Functionalization was carried out through strain-promoted alkyne–azide cycloaddition (SPAAC) between an azide dendrimer and cyclooctyne derivatives of bile acids. The cell viability and the anti-inflammatory potential of the bile acid dendrimers were evaluated in vitro and compared with those of the pure BAs. The bile acid dendrimers and pure BAs did not show significant cytotoxicity at the concentrations tested (0.78–5.00 × 104 nM) against THP-1 cells. Chenodeoxycholic acid (CDCA) and the corresponding dendrimer dendri-(CDCA)18 (polyamide dendrimer bearing 18 CDCA moieties) presented the highest anti-inflammatory activity, showing LPS-induced IL-8 release inhibition of 45.3% at 0.78 nM CDCA and 35.5% at 0.43 nM dendri-(CDCA)18.


Anti-inflammatory Bile acids Dendrimer Drug delivery Nanoparticles Nanomedicine SPAAC 


Funding information

This study is financially supported by the Sao Paulo Research Foundation – FAPESP (grant #2018/02093-0 for C.O.; PhD grant to DLB #15/04929-0), the National Council for Scientific and Technological Development – CNPq (productivity award for C.O. #307403/2018-1), and Coordination for the Improvement of Higher Education Personnel – CAPES (Ph.D. scholarship for A.M.G.P.; CAPES/DAAD Co-Financed Short-Term Research Grant Brazil, 2018 (57417991) #91674518 for A.M.G.P.). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES), finance code 001.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11051_2019_4672_MOESM1_ESM.pdf (11.3 mb)
ESM 1 NMR, infrared and mass spectra of the compounds (PDF 11.3 MB)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of ChemistryUniversity of Campinas – UnicampCampinasBrazil
  2. 2.Max Planck Institute for ChemistryMainzGermany

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