The researchers showed the interaction between the indole derivative (indole-3-aldei or 3-IAld) and the aryl hydrocarbon receptor (AhR) through computer simulation and in-vitro experiments. To define the role of AhR in the inflammation and infection, the functionality of the receptor was evaluated in a F508del homozygous FC mouse model. In these mice, receptor function decreased and appears to be associated with respiratory allergy (Aspergillus fumigatus). 3-IAld is seen to restore the activity of AhR. Researchers also showed in different models that 3-IAld has antimicrobial properties against respiratory tract bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae. Also, in in-vivo experiments on the FC mouse model exposed to Aspergillus, 3-IAld showed anti-inflammatory activity. The researchers developed a spray formulation of the compound and tested it on the in-vivo model. These tests and the results open interesting perspectives on the use of the indole derivative as a possible post-biotic drug capable of acting both on the host and on the microbes.

Pubblications

• Costantini C, Puccetti M, Pariano M et al. Selectively targeting key inflammatory pathways in cystic fibrosis, European Journal of Medicinal Chemistry, 2020 Aug 9;206:112717
• Napolioni V, Pariano M, Borghi M et al. Genetic Polymorphisms Affecting IDO1 or IDO2 Activity Differently Associate With Aspergillosis in Humans, Frontiers in Immunology, 2019; 10: 890