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[摘要]：A series of (+)-negamycin 1 analogues were synthesized, and their readthrough-promoting activity was evaluated for nonsense mutations in Duchenne muscular dystrophy 3 (DMD). A structure activity relationship study indicated that 11b was the most potent drug 0 candidate. Immunohistochemical analyses suggested that treatment with 11b restored dystrophin expression in mdx mice, a DMD mouse model. Furthermore, lib decreased serum creatine kinase (CK) levels, an indicator of muscle fiber destruction. Most importantly, 11b demonstrated lower toxicity than 1, and thus, it could be a useful candidate for long-term treatment of DMD. |
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