Article
Chemistry, Medicinal
Liqiang Hu, Huixin Yang, Tao Yu, Fangfang Chen, Runqiu Liu, Shuyuan Xue, Shuangzhan Zhang, Wuyu Mao, Changge Ji, Hao Wang, Hexin Xie
Summary: This study demonstrates the effectiveness of stereochemically altered cephalosporins as potent inhibitors against NDM-1, a major cause of antibiotic resistance. The findings provide a new approach to combat antibiotic resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Matthijs J. van Haren, Kamaleddin H. M. E. Tehrani, Ioli Kotsogianni, Nicola Wade, Nora C. Bruchle, Vida Mashayekhi, Nathaniel I. Martin
Summary: The increasing prevalence of metallo-beta-lactamase (MBL)-expressing bacteria is a worrying trend in antibiotic resistance. Studies have shown that zinc ions, which are essential for the hydrolytic activity of MBLs, can be targeted for inhibition. Researchers have developed a series of cephalosporin prodrugs that exhibit potent activity against MBLs and can act synergistically with specific antibiotics.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Ying Ge, Peng-Wei Kang, Jia-Qi Li, Han Gao, Le Zhai, Le-Yun Sun, Cheng Chen, Ke-Wu Yang
Summary: The study demonstrated that thiosemicarbazones are valuable scaffolds for developing inhibitors of NDM-1 and drug-resistant bacteria carrying NDM-1, and they also exhibit synergistic antimicrobial effects with other antibiotics, showing strong activity against bacteria harboring NDM-1.
JOURNAL OF ANTIBIOTICS
(2021)
Article
Chemistry, Medicinal
Yuwen Jia, Barbara Schroeder, Yvonne Pfeifer, Christopher Froehlich, Lihua Deng, Christoph Arkona, Benno Kuropka, Jana Sticht, Kenichi Ataka, Silke Bergemann, Gerhard Wolber, Christoph Nitsche, Martin Mielke, Hanna-Kirsti S. Leiros, Guido Werner, Joerg Rademann
Summary: Carbapenem resistance caused by metallo-β-lactamases (MBLs) such as NDM-1 is a significant threat to the effectiveness of β-lactam antibiotics. In this study, 8-hydroxy- and 8-sulfonamido-quinoline-2-carboxylic acids were developed as potent inhibitors of NDM-1 with improved activity and binding affinity. These inhibitors formed reversible protein-inhibitor complexes with two zinc ions and showed remarkable entropic gain in NDM-1 structure. They effectively reduced the minimum inhibitory concentrations (MIC) of meropenem for multidrug-resistant bacteria expressing bla (NDM-1) and clinical strains without toxicity to human cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Han Gao, Jia-Qi Li, Peng-Wei Kang, Jia-Zhu Chigan, Huan Wang, Lu Liu, Yin-Sui Xu, Le Zhai, Ke-Wu Yang
Summary: This study constructed and characterized an effective M beta L inhibitor, which showed preferential inhibition against NDM-1, potential antibacterial activities, and synergistic effects with meropenem. The research provided a new framework for the development of NDM-1 inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Microbiology
Yu-Shan Huang, Pao-Yu Chen, Pei-Chun Chou, Jann-Tay Wang
Summary: Cefiderocol and aztreonam-avibactam (ATM-AVI) both showed activity against carbapenem-resistant Gram-negative bacilli, including those that produce metallo-beta-lactamases (MBLs). However, Enterobacteriaceae isolates producing NDM carbapenemase displayed lower susceptibility to both antibiotics.
MICROBIOLOGY SPECTRUM
(2023)
Article
Materials Science, Multidisciplinary
Ayumu Kobayashi, Yoshihiro Yamaguchi, Sakura Maruki, Sunnam Kim, Yoshichika Arakawa, Seiji Kurihara
Summary: This study focuses on the enzyme inhibition by graphene oxides (GOs) on Metallo-beta-lactamase (MBL). The results show that reducing the size and oxidation degree of GOs can enhance their inhibitory capacities and alter their inhibition modes.
Article
Microbiology
Liam A. Wilson, Esmee G. Knaven, Marc T. Morris, Marcelo Monteiro Pedroso, Christopher J. Schofield, Thomas B. Brueck, Mikael Boden, David W. Waite, Philip Hugenholtz, Luke Guddat, Gerhard Schenk
Summary: The study investigates a fourth variant of metallo-beta-lactamase, SIE-1, which shows higher activity towards cephalosporins. The unusual preference of SIE-1 for cephalosporins and its presence in a widespread environmental organism suggest the potential for increased MBL-mediated beta-lactam resistance. Including SIE-1 in MBL inhibitor design studies could expand the therapeutic scope of much needed antiresistance drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Hongyan Tian, Yiwan Wang, Yang Dai, Anwen Mao, Wanqing Zhou, Xiaoli Cao, Hui Deng, Hao Lu, Lin Ding, Han Shen, Xiaojian Wang
Summary: DPASC is an effective MBL inhibitor with its block-release design strategy showing potential for the development of MBL inhibitors.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Jia-Qi Li, Le-Yun Sun, Zhihui Jiang, Cheng Chen, Han Gao, Jia-Zhu Chigan, Huan-Huan Ding, Ke-Wu Yang
Summary: A new scaffold was constructed for inhibiting NDM-1, showing promising results in combating bacterial infections and providing important insights for the development of anti-NDM-1 drugs.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Le Zhai, Yue Jiang, Yang Shi, Miao Lv, Ya-Li Pu, Hua-Lei Cheng, Jia-Yu Zhu, Ke-Wu Yang
Summary: The irregular use of antibiotics has led to the development of antibiotic-resistant bacteria, specifically metallo-beta-lactamases. This study identified eight compounds that have strong inhibitory effects on NDM-1, with one compound being the most effective inhibitor. The presence of a hydroxyl group in the compounds was found to improve their inhibitory activity. Additionally, these compounds demonstrated antibacterial effects on NDM-1-producing bacteria and showed low cytotoxicity in cell experiments.
BIOORGANIC CHEMISTRY
(2022)
Article
Infectious Diseases
Joseph Meletiadis, Paschalis Paranos, Panagiota-Christina Georgiou, Sofia Vourli, Stavroula Antonopoulou, Aikaterini Michelaki, Eleni Vagiakou, Spyros Pournaras
Summary: Metallo-beta-lactamase (MBL)-producing Gram-negative bacteria are increasing globally, with few effective agents against them. Taniborbactam is a newly developed bicyclic boronate beta-lactamase inhibitor that shows promising activity against MBL-producing isolates when used in combination with cefepime or meropenem.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Microbiology
Tomefa E. Asempa, Hannah Bajor, Jessica H. Mullins, Janice Hartnett, David P. Nicolau
Summary: Research on identifying alternative growth media that better mimic host conditions is increasing. This study evaluated meropenem susceptibility against MBL-harboring Enterobacterales strains in urine, finding lower resistance compared to conventional broth. Factors influencing zinc concentrations in urine and their impact on antibiotic resistance warrant further investigation.
MICROBIOLOGY SPECTRUM
(2021)
Article
Chemistry, Applied
Andrei Baran, Jevgenijs Kuzmins, Jevgenijs Kuznecovs, Alistair J. M. Farley, Tharindi Panduwawala, Anete Parkova, Pavel A. Donets, Jurgen Brem, Edgars Suna, Christopher J. Schofield, Kirill Shubin
Summary: We developed a new synthetic route for the preparation of metallo-beta-lactamase inhibitor pre-candidate EBL-3183 on a kilogram scale. The process involves starting from commercially available indole-2-carboxylate and using an Ellman auxiliary approach coupled with ruthenium-catalyzed stereoselective reduction to introduce chirality. The key spirocyclic cyclobutane motif was assembled using a diastereomerically pure epoxide building block. The prepared EBL-3183 was of sufficient quantity and quality for preclinical studies.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Pharmacology & Pharmacy
Bing Zhao, Xinhui Zhang, Tingting Yu, Ying Liu, Xiaoling Zhang, Yongfang Yao, Xuejian Feng, Hongmin Liu, Dequan Yu, Liying Ma, Shangshang Qin
Summary: New Delhi metallo-beta-lactamase-1 (NDM-1) poses a threat to public health as it can hydrolyze nearly all beta-lactam antibiotics. In this study, thiosemicarbazone derivatives were evaluated for their potential to treat NDM-1 positive superbugs, with compounds 19bg and 19bh showing promising activity. Molecular docking suggested these compounds may inhibit NDM-1 in an allosteric pocket, potentially offering new treatment options for NDM-1 producing strains.
ACTA PHARMACEUTICA SINICA B
(2021)
