Is magic trifluoromethyl a thing? Replacing 4-CH ₃ with 4-CF ₃ in bithiazoles, allowed to identify broad antimicrobial agents active against multiple viruses and also against Gram-positive/negative bacteria.

Background/Objectives: IBDs are chronic relapsing inflammatory intestinal disorders whose precise etiology is still only poorly defined: critical for their pathogenesis is the CCL20/CCR6 axis, whose modulation by small molecules may represent an innovative therapeutic approach. The aim of the present work is to test the potential efficacy of two molecules, MR120, a small selective CCR6 antagonist, active in TNBS- and chronic DSS-induced murine models of intestinal inflammation, and its derivative MR452, a well-tolerated agent endowed with improved anti-chemotactic in vitro properties, in the adoptive transfer colitis model. To the best of our knowledge, this is the first attempt of using adoptive transfer colitis to test modulators of the CCL20/CCR6 axis. Methods and Results: The induction of colitis in immunocompromised mice receiving CD4⁺CD25⁻ T cells i.p. resulted in a moderate inflammation and was met with limited protective responses following daily subcutaneous administration of MR120 or MR452 for 8 weeks. Both compounds significantly reduced colonic myeloperoxidase activity, MR452 also lowered CCL20 levels in the gut, but they failed to prevent the increase in disease activity index, colon wall thickening, and macroscopic inflammation score. Conclusions: Our findings suggest that the pharmacological targeting of the CCL20/CCR6 axis in the adoptive transfer model has only a modest effect in ameliorating the IBD-like phenotype driven by the altered balance between Treg and Th17. The CCL20/CCR6 inhibitors MR120 and MR452 appear more clearly involved in the control of Th1 and Th2 adaptive immune responses, as it results from the beneficial effects displayed by MR120 against subacute TNBS- and chronic DSS-induced colitis.

Background/Objectives: IBDs are chronic relapsing inflammatory intestinal disorders whose precise etiology is still only poorly defined: critical for their pathogenesis is the CCL20/CCR6 axis, whose modulation by small molecules may represent an innovative therapeutic approach. The aim of the present work is to test the potential efficacy of two molecules, MR120, a small selective CCR6 antagonist, active in TNBS- and chronic DSS-induced murine models of intestinal inflammation, and its derivative MR452, a well-tolerated agent endowed with improved anti-chemotactic in vitro properties, in the adoptive transfer colitis model. To the best of our knowledge, this is the first attempt to use adoptive transfer colitis to test modulators of the CCL20/CCR6 axis. Methods and Results: The induction of colitis in immunocompromised mice receiving CD4⁺CD25⁻ T cells i.p. resulted in a moderate inflammation and was met with limited protective responses following daily subcutaneous administration of MR120 or MR452 for 8 weeks. Both compounds significantly reduced colonic myeloperoxidase activity, and MR452 also lowered CCL20 levels in the gut, but they failed to prevent the increase in the Disease Activity Index, colon wall thickening, and macroscopic inflammation score. Conclusions: Our findings suggest that, despite the beneficial effects played by MR120 against subacute TNBS- and chronic DSS-induced colitis, the pharmacological targeting of the CCL20/CCR6 axis in the adoptive transfer model has a negligible effect in ameliorating the IBD-like phenotype driven by the altered intestinal immune homeostasis and by the disrupted function of immune-suppressive Treg cells.

Li 15 C 60 can be obtained either as a monomeric or a polymeric phase depending on the preparation conditions. A series of Raman spectra of polymer Li 15 C 60 have been acquired in the temperature range 293-565 K. The polymer starts to transform to a monomer phase at ∼420 K and the phase transition completes itself at a temperature ⩽470 K. When the monomer is formed, the Raman spectrum exhibits a charge state of C 60 −n , where 5<n<6. By lowering the temperature, the polymer phase is recovered accompanied by a considerable hysteresis. Raman results from Li 15 C 60 samples prepared through other preparation routes that favor the stabilization of different monomer/polymer C 60 phases are also presented, correlated with their corresponding X-ray diffraction structural data and discussed. Comparison with Li 27 C 60 results is also discussed.