Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)

Jiachi Chiou; Shengbiao Wan; Kin-Fai Chan; Pui-Kin So; Dandan He; Edward Wai-chi Chan; Tak-hang Chan; Kwok-yin Wong; Jiang Tao; Sheng Chen

doi:10.1039/C5CC02594J

Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)†

Jiachi Chiou,‡^ab Shengbiao Wan,‡^c Kin-Fai Chan,^b Pui-Kin So,^b Dandan He,^ab Edward Wai-chi Chan,^ab Tak-hang Chan,^b Kwok-yin Wong,^b Jiang Tao*^c and Sheng Chen*^ab

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* Corresponding authors

^a Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong Polytechnic University, Shenzhen Research Institute, Shenzhen, P.R. China
E-mail: sheng.chen@polyu.edu.hk
Fax: +852-2364 9932
Tel: +852-3400-8795

^b State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

^c Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China
E-mail: jiangtao@ouc.edu.cn
Fax: +86-532-82033054
Tel: +86-532-82032712

Abstract

We report the discovery of a promising NDM-1 inhibitor, ebselen, through a cell-based screening approach. Enzymatic kinetic study and ESI-MS analysis suggested that ebselen could bind to NDM-1 by forming a S–Se bond with the Cys²²¹ residue at the active site, thereby exhibiting a new inhibition mechanism with broad spectrum inhibitory potential.

Chemical Communications

Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)†

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Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)

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