In vitro co-culture studies and the crucial role of fibroblast-immune cell crosstalk in IPF pathogenesis

Abstract IPF is a fatal lung disease characterized by intensive remodeling of lung tissue leading to respiratory failure. The remodeling in IPF lungs is largely characterized by uncontrolled fibrosis. Fibroblasts and their contractile phenotype the myofibroblast are the main cell types responsible for typical wound healing responses, however in IPF, these responses are aberrant and result in the overactivation of fibroblasts which contributes to the inelasticity of the lung leading to a decrease in lung function. The specific mechanisms behind IPF pathogenesis have been elusive, but recently the innate and adaptive immunity have been implicated in the fibrotic processes of the disease. In connection with this, several in vitro co-culture models have been used to investigate the specific interactions occurring between fibroblasts and immune cells and how this contributes to the pathobiology of IPF. In this review, we discuss the in vitro models that have been used to examine the abnormal interactions between fibroblasts and cells of the innate and adaptive immune system, and how these contribute to the fibrotic processes in the lungs of IPF patients

Syntheses and crystal structure of 4-[(pyridin-3-yl)diazen­yl]morpholine and 1-[(pyridin-3-yl)diazen­yl]-1,2,3,4-tetra­hydro­quinoline

Two new heterocyclic 1,2,3-triazenes were synthesized by diazo­tation of 3-amino­pyridine following respectively by coupling with morpholine or 1,2,3,4-tetra­hydro­quinoline. 4-[(Pyridin-3-yl)diazen­yl]morpholine (I), C9H12N4O, has monoclinic P21/c symmetry at 100 K, while 1-[(pyridin-3-yl)diazen­yl]-1,2,3,4-tetra­hydro­quinoline (II), C14H14N4, has monoclinic P21/n symmetry at 100 K. These 1,2,3-triazene derivatives were synthesized by the organic medium method by coupling reactions of 3-amino­pyridine with morpholine and 1,2,3,4-tetra­hydro­quinoline, respectively, and characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and single-crystal X-ray diffraction. The mol­ecule of compound I consists of pyridine and morpholine rings connected by an azo moiety (–N=N–). In the mol­ecule of II, the pyridine ring and the 1,2,3,4-tetra­hydro­quinoline unit are also connected by an azo moiety. The double- and single-bond distances in the triazene chain are comparable for the two compounds. In both crystal structures, the mol­ecules are connected by C—H⋯N inter­actions, forming infinite chains for I and layers parallel to the bc plane for II

Evaluation of antibacterial and antifungal activities of N-benzylthienopyrimidinone derivatives

This study is part of the biological investigation of the chemical library of molecules already described by the Laboratory of Organic Chemistry and Therapeutic Chemistry of the University of Bordeaux. The main objective was to explore the contribution of a thienyl moiety attached to the pyrimidinone nucleus, in the expression of an antimicrobial activity. The structural modifications mainly concerned the conservation or not of  the  benzo fragment attached to the thienyl, the saturation or not in position-1,2 of the pyrimidinone ring, the substitution on N-benzyl with more or less lipophilic units, the modification of the orientation of the thienyl fragment with, on  the one hand, the compounds in which the sulfur is located near the N1 nitrogen (series of thieno[2,3-d]pyrimidin-4-ones) and on the other hand, compounds in which the sulfur is located near the ketone group (series of thieno[3,2-d]pyrimidin-4-ones). In general, thienyl fragment with sulfur located near the ketone group and the unsaturated pyrimidinone nucleus in the 1,2-position, seem to promote a broad spectrum of antibacterial activity, with compound 9c which is active on both Gram + bacteria and Gram – bacteria studied. The same pattern was observed for antifungal activity, which is maximum with the compounds of the thieno[3,2-d]pyrimidin-4-ones series for an MIC of 31.25 μg/ml on the strains of Candida albicans and Candida kruzei studied. Keywords: Thienopyrimidinones, antibacterial activity, antifungal activity

Neko Sac

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Ma Cherie

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Aduna

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Seey

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