March 6, 2025
Keio University
Tohoku University
Institute of Microbial Chemistry
A research group, including Associate Professor Daisuke Takahashi and Professor Kazunobu Toshima of the Department of Applied Chemistry, Faculty of Science and Technology, Keio University; Assistant Professor Takeshi Yokoyama of the Graduate School of Life Sciences, Tohoku University; and Dr. Masayuki Igarashi of the Institute of Microbial Chemistry, has developed a novel chemical modification method for the macrolide antibiotic azithromycin (AZM). By utilizing this method, they have successfully created a new lead compound for treating pulmonary nontuberculous mycobacterial (NTM) disease.
AZM is widely used for the treatment of pulmonary NTM disease, which is caused by NTM infection in the lungs. However, the emergence of drug-resistant bacteria has created a strong demand for the development of new therapeutic drugs. In this study, the research group established a method for the rapid synthesis of novel AZM derivatives and successfully synthesized a library using their originally developed regio- and stereoselective glycosylation reaction. Furthermore, evaluation of the antibacterial activity of the synthesized library against NTM revealed that the derivative KU13 exhibits higher antibacterial activity than AZM against both drug-susceptible and drug-resistant NTM, identifying it as a promising new drug candidate for pulmonary NTM disease. Analysis of its mechanism of action also revealed a unique mechanism, where the derivative induces a structural change in its target molecule, the ribosome, while forming new interactions. This discovery is expected to contribute to the development of new treatments for pulmonary NTM disease that are effective against drug-resistant NTM.
The results of this research were published in the American multidisciplinary scientific journal "Science Advances" on March 5, 2025.
The full press release can be found below.