Multi-task evaluation of TMA analogues as anti-inflammatory treatments for CF lung disease

Principal objective of the project (FFC #22/2019, PI: Prof. Ilaria Lampronti) was the implementation of the knowledge on new-generation TMA analogues, in order to develop new drugs for the CF pulmonary disease, through the evaluation of simultaneous dualistic activity (anti-inflammatory and modulating activities). Since the transcription factor NF-kB plays a critical role in IL-8 expression, the use of agents able to interfere with the NF-kB pathway represents an interesting therapeutic strategy (Cabrini G, 2020). All our research was aimed at designing and developing molecules capable of acting both as anti-inflammatories, inhibiting the NF-kB pathway, and as CFTR correctors, in order to obtain a single drug with double activity in the future. The experimental plan was focalized on in vitro and in vivo models to deeply and fully study the new psoralen derivatives. Of course, another key objective was to check that both the in vitro and in vivo side effects were absent, or at least very attenuated. In addition to the planned experiments, we also tested our analogues using numerous in vitro and in vivo assays (described in the “Results” chapter) to obtain reliable results. The study of the possible synergism between selected TMA derivatives and other known anti-inflammatory (Ibuprofen) or anti-microbial (Tobramycin, Colistin, Ciprofloxacin and Azithromycin) agents currently used in CF patients was performed. Finally, our goal was to start the process leading to possible patent protection and exploitation or to the orphan drug designation (ODD) of one TMA derivative in order to finalize our research by the develop of a product with relevant biological activity for the CF treatment and attractive for industrial partners.