Drug Repurposing by Siderophore Conjugation: Synthesis and Biological Evaluation of Siderophore‐Methotrexate Conjugates as Antibiotics

• Published in: Angewandte Chemie International Edition Vol. 61; no. 36; pp. e202204139 - n/a
• Main Authors: Zhao, Sheng, Wang, Zhi‐Peng, Lin, Zihua, Wei, Guoxing, Wen, Xumei, Li, Siyu, Yang, Xiaohong, Zhang, Qun, Jing, Chunmei, Dai, Yuanwei, Guo, Jian, He, Yun
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 05.09.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Antibiotics; Antimicrobial resistance; Antimicrobials; Antineoplastic drugs; Antitumor agents; Chemistry; Chemistry, Multidisciplinary; Conjugate; Conjugates; Conjugation; Cytotoxicity; Dihydrofolate reductase; Drug Repurpose; Methotrexate; Minimum inhibitory concentration; Permeability; Physical Sciences; Reductases; Science & Technology; Siderophore; Streptococcus pneumoniae; Toxicity; IRON UPTAKE; Conjugate; Siderophore; Antimicrobials; CATECHOL; Drug Repurpose; SYSTEMS; Methotrexate; ALBOMYCIN

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...