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- W4284959861 abstract "Drug repurposing is considered a promising strategy to fight antimicrobial resistance (AMR). Methotrexate (Mtx), a classical anticancer drug, could strongly inhibit bacterial dihydrofolate reductase (DHFR). However, its poor permeability into bacteria and potent human cytotoxicity make it unsuitable as an antibacterial. Herein, we reported the conjugation of Mtx with a siderophore to construct Trojan horse antibacterials. The most potent conjugate 8 with nanomolar minimum inhibitory concentration (MIC) values exhibited over 1.00×103 -fold improved activity against Gram-positive Streptococcus pneumoniae (S. pneumoniae) and Gram-negative Yersinia enterocolitica (Y. enterocolitica) compared with Mtx, while possessing 2.31×103 -fold reduced human cytotoxicity, resulting in 2.08×106 -fold improvements in the therapeutic index. This proof-of-principle study verifies that siderophore conjugation is an effective strategy for developing new antibacterials from anticancer drugs." @default.
- W4284959861 created "2022-07-10" @default.
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- W4284959861 date "2022-07-25" @default.
- W4284959861 modified "2023-10-15" @default.
- W4284959861 title "Drug Repurposing by Siderophore Conjugation: Synthesis and Biological Evaluation of Siderophore‐Methotrexate Conjugates as Antibiotics" @default.
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- W4284959861 doi "https://doi.org/10.1002/anie.202204139" @default.
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