The major objective of the project is to test TMA analogs with the aim offinding new antinflammatory agents and/or CFTR function modulators with equal or higher activity in respect to the parent TMA, and with absent DNA photobinding properties. In addition, the newly synthesized compounds will allow to derive structure-activity relationships on both the biological activities on inflammation and CFTR modulation. The goals of the project can be outlined in 5 sections: 1) design and synthesis of new TMA analogs; 2) test of photoreactivity; 3) test of the anti-inflammatory activity, based on inhibition of NFkB/ DNA interaction and expression of pro-inflammatory genes in CF bronchial cell lines and 4) test of the effects as CFTR function modulation; 5) derivation of structure-activity relationships aimed at rationalizing the structural determinants required to obtain selective anti-inflammatory properties, selective CFTR modulatory properties and dual antiinflammatory/ CFTR modulatory activity.