Vol.67 No.3 May 2019
Search for new antibiotics from natural products
Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, Japan
Abstract
The emergence and spread of antibiotic-resistant bacteria is a worldwide problem that necessitates countermeasures at both the national and international levels. In Japan, a drug resistance action plan was formulated in 2016 that included research and development of new antibiotics against drug-resistant bacterial infections. In the field of infectious diseases, many of the launched drugs are derived from natural products; therefore, much effort is being focused on drug discovery from natural products. The Institute of Microbiological Chemistry (BIKAKEN) was founded in 1957 by Dr. Hamao Umezawa, triggered by the discovery of kanamycin. Since then, BIKAKEN has set up drug discovery from natural products as the focus of its activities and has introduced many antibiotics to the world.
Recently, some attractive new natural products have been discovered in BIKAKEN. In this review, the authors present an overview of these new compounds: nybomycin, amycolamicin, signamycin B, and intervenolin. These compounds have different mechanisms of action as compared to the antibiotics launched until now and can be considered as useful tools against resistant bacteria. In addition, we shall introduce the discovery and development of CPZEN-45, an antituberculous drug against extremely multidrug-resistant tuberculosis, which inhibits the process of arabinogalactan biosynthesis in Mycobacterium tuberculosis, and is derived from the antibiotic caprazamycin. We shall also introduce the new-generation aminoglycoside antibiotic, TS3112, which has been shown to be effective against super multidrug-resistant Gram-negative bacteria, such as carbapenem-resistant enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa. BIKAKEN aims to continue to be a pillar for drug discovery from natural products in Japan in the future too.
Key word
antimicrobial resistance, natural product, antibiotics, CPZEN-45, TS3112
Received
September 26, 2018
Accepted
November 15, 2018
Jpn. J. Chemother. 67 (3): 308-323, 2019
