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ID: ALA4138160

Journal: Eur J Med Chem

Title: Biphenylthiazole antibiotics with an oxadiazole linker: An approach to improve physicochemical properties and oral bioavailability.

Authors: Hagras M, Hegazy YA, Elkabbany AH, Mohammad H, Ghiaty A, Abdelghany TM, Seleem MN, Mayhoub AS.

Abstract: A new series of oxadiazolylbiphenylthiazoles was prepared with the objective of improving the limited solubility of first-generation derivatives while maintaining antibacterial activity against drug-resistant Staphylococcus aureus. Studying the structure-activity relationship at the cationic part provided the piperazine-1-carboximidamide derivative 27 with a MIC (MRSA) value of 1.1 μg/mL, bactericidal mode of action, and a 50-fold improvement in aqueous solubility. Additionally, 27 exhibited a wider safety margin against mammalian cells, and most importantly, a significant improvement in oral bioavailability.

CiteXplore: 29126738

DOI: 10.1016/j.ejmech.2017.10.048