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https://www.selleckchem.com/products/gcn2-in-1.html Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.Hypoxia is one of key characteristics of microenvironments of solid tumors, and evaluation of hypoxia status in solid tumors
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