Adduct Formation of Delamanid with NAD in Mycobacteria-Reference-Cited by-同舟云学术

Adduct Formation of Delamanid with NAD in Mycobacteria

Published:2020-04-21 Issue:5 Volume:64 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Hayashi Mikayo¹,Nishiyama Akihito²,Kitamoto Ryuki¹,Tateishi Yoshitaka²,Osada-Oka Mayuko²³,Nishiuchi Yukiko⁴,Kaboso Shaban A.²,Chen Xiuhao¹,Fujiwara Mamoru¹,Inoue Yusuke¹,Kawano Yoshikazu¹,Kawasaki Masanori¹,Abe Tohru⁵,Sato Tsutomu⁵,Kaneko Kentaro⁶,Itoh Kimiko⁶,Matsumoto Sohkichi²⁷^ORCID,Matsumoto Makoto¹

Affiliation:

1. Pharmaceutical Business Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan

2. Department of Bacteriology, Niigata University School of Medicine, Niigata, Japan

3. Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan

4. Toneyama Institute for Tuberculosis Research, Osaka City University Medical School, Osaka, Japan

5. Department of Applied Biological Chemistry, Faculty of Agriculture and Graduate School of Science and Technology, Niigata University, Niigata, Japan

6. Graduate School of Science and Technology, Niigata University, Niigata, Japan

7. Laboratory of Tuberculosis, Institute of Tropical Disease, Universitas Airlangga, Mulyorejo, Surabaya, Indonesia

Abstract

Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F 420 )-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated Mycobacterium tuberculosis var.

Funder

Japan Agency for Medical Research and Development

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01755-19

Reference28 articles.

1. World Health Organization. 2018. Global Tuberculosis Report 2018. WHO, Geneva, Switzerland.

2. OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

3. Substrate specificity of the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis responsible for the bioreductive activation of bicyclic nitroimidazoles