The intestinal microbiota is a major factor in human health and disease. This microbial community includes autochthonous (permanent inhabitants) and allochthonous (transient inhabitants) microorganisms that contribute to maintaining the integrity of the intestinal wall, modulating responses to pathogenic noxae and representing a key factor in the maturation of the immune system. If this healthy microbiota is disrupted by antibiotics, chemotherapy, or a change in diet, intestinal colonization by pathogenic bacteria or viruses may occur, leading to disease. To manage substantial microbial exposure, epithelial surfaces of the intestinal tract produce a diverse arsenal of antimicrobial peptides (AMPs), including, of considerable importance, the β-defensins, which directly kill or inhibit the growth of microorganisms. Based on the literature data, the purpose of this work was to create a line of intestinal epithelial cells able to stably express gene encoding human β-defensin-2 (hBD-2) and human β-defensin-3 (hBD-3), in order to test their role in S. typhimurium infections and their interaction with the bacteria of the gut microbiota.
A visible-light-promoted three-component isocyanide-based synthesis of iminofurans is herein reported. The reaction proved to be general in scope and proceeds through a triple domino process. Control experiments with 18 O-labeled water and TEMPO provided key mechanistic insights for delineating the reactivity paradigms crucial to design efficient photoredox isocyanide-based domino transformations.
Privileged scaffolds as starting points toward biologically active molecules represent a neuralgic point in drug discovery. The ability of synthetic chemists concerned with their generation should be flanked by robust...
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