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)
Review
Chemistry, Multidisciplinary
Yang Ding, Zheng Li, Chenchen Xu, Wenjing Qin, Qiong Wu, Xuchun Wang, Xiamin Cheng, Lin Li, Wei Huang
Summary: Beta-lactam antibiotics are important inventions in treating infections, but the emergence of beta-lactamase in bacteria leads to drug resistance. Various detection methods and inhibitors are available, and designing improved probes may help overcome bacterial resistance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Peixin Fan, Zhengxin Ma, Arianna J. Partow, Miju Kim, Grace M. Shoemaker, Ruwen Tan, Zhaohui Tong, Corwin D. Nelson, Yeongseon Jang, Kwangcheol C. Jeong
Summary: Antimicrobial resistance poses a major global threat, especially multidrug resistant ESBL-producing pathogens. Researchers developed a novel therapy combining cephalosporin antibiotics and beta-lactamase inhibitors encapsulated in chitosan nanoparticles, effectively combating drug-resistant Enterobacteriaceae and showing promising potential for treating critically important infections.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Pharmacology & Pharmacy
Yuejuan Zhang, Cheng Chen, Bin Cheng, Lei Gao, Chuan Qin, Lixia Zhang, Xu Zhang, Jun Wang, Yi Wan
Summary: Carbapenem resistance caused by OXA-48 beta-lactamase is a global health threat. In this study, quercetin and its analogs were identified as potent inhibitors of OXA-48, with the ability to restore the antibacterial efficacy of certain antibiotics against OXA-48-producing bacteria. Mechanism studies revealed that these compounds interacted with OXA-48 through hydrogen bonding, leading to the inhibition of its activity. Additionally, quercetin showed antimicrobial activity in combination with certain antibiotics in a mouse infection model.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Infectious Diseases
Davide Carcione, Claudia Siracusa, Adela Sulejmani, Valerio Leoni, Jari Intra
Summary: Beta-lactams are important antibiotics, but increasing resistance, especially among Gram-negative bacteria, poses a major threat to public health. Combining beta-lactam antibiotics with beta-lactamase inhibitors can help overcome resistance, but some beta-lactamases are resistant to existing inhibitors, leading to a need for new and more efficient inhibitors.
Article
Microbiology
Fredrika Rajer, Lisa Allander, Philip A. Karlsson, Linus Sandegren
Summary: β-lactam antibiotics are the first choice for the treatment of bacterial infections, but the prevalence of β-lactamases limits their effectiveness. Combining β-lactam antibiotics with β-lactamase inhibitors can restore treatment efficacy. However, clinical isolates often carry multiple β-lactamases and other resistance genes, which impact the development of resistance.
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
Microbiology
Khalid M. Dousa, David C. Nguyen, Sebastian G. Kurz, Magdalena A. Taracila, Christopher R. Bethel, William Schinabeck, Barry N. Kreiswirth, Sheldon T. Brown, W. Henry Boom, Richard S. Hotchkiss, Kenneth E. Remy, Frank J. Jacono, Charles L. Daley, Steven M. Holland, Alita A. Miller, Robert A. Bonomo
Summary: Mycobacterium abscessus (Mab) infections pose a growing threat to patients, especially those with lung diseases and cystic fibrosis. Finding effective combinations of beta-lactam antibiotics and beta-lactamase inhibitors to disrupt cell wall synthesis in Mab is beneficial. The novel diazobicyclooctane beta-lactamase inhibitor durlobactam (DUR) enhances the susceptibilities of Mab isolates to beta-lactams in cell-based assays. DUR potently inhibits the beta-lactamase Bla(Mab) and forms stable acyl-enzyme complexes, providing a biochemical rationale for its activity.
Article
Microbiology
Khalid M. Dousa, David C. Nguyen, Sebastian G. Kurz, Magdalena A. Taracila, Christopher R. Bethel, William Schinabeck, Barry N. Kreiswirth, Sheldon T. Brown, W. Henry Boom, Richard S. Hotchkiss, Kenneth E. Remy, Frank J. Jacono, Charles L. Daley, Steven M. Holland, Alita A. Miller, Robert A. Bonomo
Summary: Mycobacterium abscessus (Mab) infections are a growing threat to health, but combining DUR with beta-lactams can restore drug susceptibility. The triple drug combinations of CXM-DUR-AMOX and IMI-DUR-AMOX were the most effective in enhancing susceptibility.
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)
Review
Infectious Diseases
Souha S. Kanj, Matteo Bassetti, Pattarachai Kiratisin, Camilla Rodrigues, Maria Virginia Villegas, Yunsong Yu, David van Duin
Summary: Multidrug-resistant Gram-negative bacteria pose a critical threat to healthcare. New antibiotics and combination therapies, including ceftazidime-avibactam, meropenem-vaborbactam, and ceftolozane-tazobactam, have shown effectiveness in treating these infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
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
Chemistry, Medicinal
Alice Legru, Federica Verdirosa, Jean-Francois Hernandez, Giusy Tassone, Filomena Sannio, Manuela Benvenuti, Pierre-Alexis Conde, Guillaume Bossis, Caitlyn A. Thomas, Michael W. Crowder, Melissa Dillenberger, Katja Becker, Cecilia Pozzi, Stefano Mangani, Jean-Denis Docquier, Laurent Gavara
Summary: Metallo-beta-lactamases (MBLs) play a significant role in the resistance of Gram-negative bacteria to beta-lactam antibiotics. Researchers have explored compounds as broad-spectrum inhibitors of MBLs and found promising results in in vitro antibacterial susceptibility assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jia-Zhu Chigan, Zhenxin Hu, Lu Liu, Yin-Sui Xu, Huan-Huan Ding, Ke-Wu Yang
Summary: The superbug infection caused by metallo-beta-lactamases (M beta Ls) has become an urgent health threat. In this study, compounds were synthesized and tested for their inhibitory effect on M beta L NDM-1. Among them, 1e and 1f showed the strongest inhibition, with an IC50 value of 0.02 mu M against NDM-1. This study provides potential lead compounds for further development of clinically useful inhibitors targeting NDM-1.
BIOORGANIC CHEMISTRY
(2022)
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)