Title:Inhibition of IL-2 Production by Novel Small Molecules using Building Blocks from Reduced Chalcones and a Substituted Proline
Volume: 13
Issue: 2
Author(s): Esteban F. Duran-Lara*, Wender A. da Silva, Luis Guzman, Ricardo Castro, Carlos Kleber Z. Andrade and Leonardo S. Santos
Affiliation:
- Biomaterials Laboratory, Drug Delivery and Controlled Release, Department of Microbiology, Faculty of Health Sciences, University of Talca, Talca,Chile
Keywords:
Chalcones, N-substituted L-proline, IL-2 production, immunosuppressants, small molecules,
stereoselectivity.
Abstract: Background: Immunosuppressants are a class of drugs that can inhibit the
immune response, mainly through the inhibition of IL-2 production, among other
mechanisms. The most studied representatives of this class of therapeutic agents are Cyclosporin-
A, FK506, and Rapamycin. Due to the structural complexity of these molecules,
their chemical synthesis has been difficult and expensive.
Objective: To synthesize novel small molecules that are structurally simple and that can
be inhibitors of IL-2 production. These molecules are proposed to constitute new hypothetic
immunosuppressant agents.
Method: These small molecules were obtained through simple, cheap and efficient
methods of well-known synthetic transformations. The molecules were synthetized in
few steps through a highly convergent route and produced high yields.
Results: Among the six compounds synthetized, compounds 4a1 and 4b2 showed interesting
inhibitory activity. At higher concentration, compound 4a1 showed significant activity.
However, the isomer 4a2 showed considerably less activity than 4a1, perhaps, for
the high stereoselectivity ligand-receptor. Furthermore, the evaluation of the effect of
novel molecules on the viability of mononuclear cells was carried out. The effect of the
molecules proved to be innocuous.
Conclusion: The data obtained from the inhibition of IL-2 production and low toxicity
in mononuclear cells are promising for the development of future studies on these new
hypothetic immunosuppressant agents.
