Tyrosyl-tRNA synthetase inhibitors: a patent review

ABSTRACT

Introduction: Bacterial infection has been a consistent and relentless threat to human health because of emerging resistance to existing antibiotics. Therefore, much of the research has been focused on the design of new potent antibacterial agents. Tyrosyl-tRNA synthetase (TyrRS), as a member of aminoacyl-tRNA synthetase family, could recognize the information including the coincident tRNA molecules and the amino acids’ structures, which are essential in translating the coded information into protein structures in nucleic acids. Therefore, the discovery and application of tyrosyl-tRNA synthetase inhibitors might be a potential strategy to control these diseases in humans.

Areas covered: This review covers 1999 to 2016 wherein several new analogues were claimed as TyrRS inhibitors based on their chemical structures. Xiao, Z.P. et al patented two Chinese patents related to TyrRS inhibitors which are included.

Expert opinion: Due to the pivotal role in translation, tyrosyl-tRNA synthetase has been recognized as a promising target for a new generation of antibiotics with selectivity and specificity. However, while some of the TyrRS inhibitors showed encouraging results, there is an urgent need to develop novel TyrRS inhibitors with higher activity and selectivity. Based on the published SAR results, selective tyrosyl-tRNA synthetase inhibitors could be designed and developed as the next generation of antibacterial agents.

KEYWORDS:

• TyrRS
• antibacterial agents
• inhibitors
• arylfuran
• adenosine
• metronidazole

Article highlights

• Tyrosyl-tRNA synthetase is a vital and attractive target for development of new antimicrobial agents.

• Many kinds of TyrRS inhibitors have been reported. They can be categorized into different classes according to their structures.

• Furan-2(5H)-one derivatives containing ester group maybe a new skeleton for broad antimicrobial agents

• A series of metronidazole derivatives containing piperazine group show strong antibacterial activity with IC₅₀ values in the nanomolar range.

• These TyrRS inhibitors could possibly be novel effective drugs for antimicrobial activities.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work is supported by National Science and Technology Support Project (No. 2015BAD16B07), Natural Science Foundation of Jiangsu Province (BK20160570), and Jiangsu Planned Project for Postdoctoral Research Funds (1601041A).