Article
Chemistry, Medicinal
Yong-Jun Huang, Xiao-Lin Zhong, Yi-Peng Zang, Ming-Han Yang, Jing Lin, Wei -Min Chen
Summary: The natural prenylated chalcone isobavachalcone (IBC) is effective against Gram-positive bacteria but not Gram-negative bacteria due to the outer membrane barrier. In this study, conjugates of 3-hydroxy-pyridin-4(1H)-ones and IBC were designed and synthesized based on the Trojan horse strategy. The conjugates showed lower MICs and IC50s against Pseudomonas aeruginosa PAO1 and MDR strains compared to IBC, and their antibacterial activity was regulated by the bacterial iron uptake pathway.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jun Liu, Ying Meng, Ming-Han Yang, Xiao-Yi Zhang, Jian-Fu Zhao, Ping-Hua Sun, Wei-Min Chen
Summary: In this study, several 3-hydroxypyridin-4(1H)-one hybrids were designed and synthesized, and their potential as inhibitors of P. aeruginosa biofilm formation was evaluated. The most active compound, 12h, exhibited significant biofilm inhibitory activity. Mechanistic studies revealed that 12h inhibited biofilm formation by suppressing the expression of lasB and pqsA. Furthermore, 12h improved the antibiotic susceptibility of P. aeruginosa and reduced its acute virulence in Vero cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shen Mao, Qiaoqiang Li, Zhikun Yang, Yasheng Li, Xinyi Ye, Hong Wang
Summary: In this paper, six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa quorum sensing inhibitors. The experimental results showed that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies revealed that 6b mainly acted as a quorum sensing inhibitor through the las system. Silico molecular docking studies demonstrated the molecular binding between 6b and the P. aeruginosa quorum sensing receptor LasR via hydrogen bonding interactions. The structure-activity relationship and docking studies suggested the potential of 6b as anti-biofilm compounds for further studies on microbial resistance.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Juan Marcos Oliveras, Raimon Puig de la Bellacasa, Roger Estrada-Tejedor, Jordi Teixido, Jose Borrell
Summary: 1,6-Naphthyridin-2(1H)-ones, a subfamily of naphthyridines, consist of over 17,000 compounds with various substituents at key positions. This review explores the synthetic methods and biomedical applications of these compounds, as well as the diversity in substituents at positions N1, C3, C4, C5, C7, and C8.
Article
Infectious Diseases
Taehyeong Lim, So-Young Ham, SangJin Nam, Myoungsun Kim, Ki Yong Lee, Hee-Deung Park, Youngjoo Byun
Summary: This article reviews recent studies on small molecules targeting the RhlI/RhlR system in P. aeruginosa, discussing their in vitro and in vivo biological activities. The article focuses on structure-activity relationship studies and the outlook for next-generation anti-biofilm agents.
Article
Biotechnology & Applied Microbiology
James Redfern, Janine Wallace, Alex van Belkum, Magali Jaillard, Elliot Whittard, Roobinidevi Ragupathy, Joanna Verran, Peter Kelly, Mark Charles Enright
Summary: Pseudomonas aeruginosa is a common environmental microorganism that can form biofilms on indwelling device surfaces, promoting adhesion and survival. Research identified accessory genes and core-genome SNPs associated with enhanced biofilm production at 22 degrees C, including a 165 kb genomic island with heavy metal resistance genes.
Article
Infectious Diseases
Tomasz Bogiel, Dagmara Depka, Mateusz Rzepka, Joanna Kwiecinska-Pirog, Eugenia Gospodarek-Komkowska
Summary: The study investigated the frequency and genotype distribution of 10 virulence factor genes in 107 non-duplicated carbapenem-resistant P. aeruginosa isolates. Variations were observed in the prevalence and distribution of virulence genes, especially in terms of their carbapenemase synthesis ability and the strain origin.
Article
Biology
Steffen Geisel, Eleonora Secchi, Jan Vermant
Summary: Biofilms are bacterial communities encased by a self-produced matrix, and the channel networks formed within the biofilm play a vital role in promoting the transport of nutrients and chemicals. This study focuses on the role of the biofilm matrix adhesion in channel formation, specifically in Pseudomonas aeruginosa biofilms grown under constant flow in microfluidic channels. The formation of wrinkles and folds is triggered by a mechanical buckling instability, resulting in hollow channels that facilitate bacterial movement.
Review
Biotechnology & Applied Microbiology
Anming Xu, Xiaoxiao Zhang, Tong Wang, Fengxue Xin, Luyan Z. Ma, Jie Zhou, Weiliang Dong, Min Jiang
Summary: Pseudomonas aeruginosa is known for its excellent ecological flexibility and can survive in diverse niches. The adaptive mutants RSCVs have been frequently isolated from chronic infections, sparking interest in investigating their formation, persistence, and pathogenesis. RSCVs are believed to play a significant role in biofilm formation and high adaptability.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Chemistry, Multidisciplinary
Olesja Koleda, Tobias Prenzel, Johannes Winter, Tomoki Hirohata, Maria de Jesus Galvez-Vazquez, Dieter Schollmeyer, Shinsuke Inagi, Edgars Suna, Siegfried R. Waldvogel
Summary: Cathodic synthesis enables the sustainable access to 1-hydroxy- and 1-oxy-quinazolin-4-ones utilizing easily accessible nitro starting materials. This method features mild reaction conditions, inexpensive and reusable carbon-based electrode materials, an undivided electrochemical setup, and constant current conditions. The use of sulphuric acid as a supporting electrolyte and cyclization catalyst, along with the broad applicability demonstrated with 27 differently substituted derivatives achieving high yields (up to 92%), emphasizes its significance for preparative applications. Mechanistic studies based on cyclic voltammetry measurements reveal the selective reduction of nitro substrates to hydroxylamines as a crucial step.
Article
Chemistry, Multidisciplinary
Xiaodie Yuan, Xia Zhao, Yuan Lin, Zhaohui Su
Summary: This study synthesized PDA nanoparticles of various sizes and introduced different surface groups to investigate their penetration and accumulation abilities in biofilms. The PDA nanoparticles of approximately 60 nm size showed higher penetration and accumulation abilities, and the positively charged amine groups were more effective in enhancing the interactions with the biofilm compared to carboxyl or methoxy groups. The PDA60 nanoparticles with amine surface groups also exhibited good photothermal properties.
Article
Infectious Diseases
Emilie Charpentier, Ludovic Doudet, Ingrid Allart-Simon, Marius Colin, Sophie C. Gangloff, Stephane Gerard, Fany Reffuveille
Summary: The combination of non-antimicrobial molecules with antibiotics can significantly reduce bacterial biofilm formation, potentially offering a solution to combat antibiotic resistance emergence.
Article
Chemistry, Medicinal
Yuan -Yuan Wang, Xiao-Yi Zhang, Xiao-Lin Zhong, Yong-Jun Huang, Jing Lin, Wei -Min Chen
Summary: We report a series of 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates designed as dual antibacterial and antibiofilm agents against Pseudomonas aeruginosa. The 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1H)-one-ciprofloxacin conjugate (5e) showed the best minimum inhibitory concentrations and reduced biofilm formation by 78.3%. Additionally, 5e eradicated mature biofilms and killed living bacterial cells within the biofilm. Mechanistic studies revealed that 5e interfered with iron uptake, inhibited motility, and reduced virulence production. These findings highlight the potential of 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates for treating biofilm-associated drug-resistant Pseudomonas aeruginosa infections.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Davoodbasha MubarakAli, Kannappan Arunachalam, Murugan Lakshmanan, Bazigha Badar, Jung-Wan Kim, Sang-Yul Lee
Summary: Biofilm-related nosocomial infections can cause various life-threatening infections. In this study, hydroxyapatite nanoparticles (HANPs) were synthesized using a co-precipitation method followed by microwave treatment, and their ability to inhibit the biofilm formation of Pseudomonas aeruginosa ATCC 10145 was investigated. The results showed that the synthesized HANPs effectively inhibited biofilm formation, suggesting their potential use in controlling biofilm-related infections caused by Pseudomonas aeruginosa.
Article
Immunology
Zuoji Ye, Liumei Ye, Dingbin Li, Shunsheng Lin, Wusheng Deng, Li Zhang, Jinhua Liang, Jinlong Li, Qingjun Wei, Ke Wang
Summary: In this study, the researchers found that Daphnetin (DAP) can effectively inhibit and eradicate biofilm formation of Pseudomonas aeruginosa. DAP also reduced bacterial motility and pyocyanin production. These findings suggest that DAP may serve as a natural anti-biofilm therapeutic agent.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Kuo Lu, Qi Chen, Xiao-Fang Xu, Ying Meng, Jing Lin, Wei-Min Chen
JOURNAL OF ANTIBIOTICS
(2020)
Article
Chemistry, Medicinal
Kuo Lu, Wen Hou, Xiao-Fang Xu, Qi Chen, Zhengqiu Li, Jing Lin, Wei-Min Chen
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Teng-Fei Xuan, Zi-Qiang Wang, Jun Liu, Hai-Tao Yu, Qian-Wen Lin, Wei-Min Chen, Jing Lin
Summary: The study proposed a new antibiofilm strategy involving the induction of dysfunctional G-quadruplexes by c-di-GMP to block the biofilm regulatory pathway. Compound 5h exhibited favorable c-di-GMP G-quadruplex-inducing and biofilm inhibitory activities, without any DNA intercalation effect. The performance of 5h in interfering with c-di-GMP-related biological functions was confirmed through reporter strain and transcriptome analysis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jia-Hui Yu, Xiao-Fang Xu, Wen Hou, Ying Meng, Mei-Yan Huang, Jing Lin, Wei-Min Chen
Summary: The study synthesized 37 new derivatives of cajaninstilbene acid (CSA), with 23 showing a tendency to eradicate MRSA persisters and exhibiting stronger antimicrobial properties against S. aureus and MRSA compared to CSA. A representative compound (A6) targeted bacterial cell membranes, effectively reducing the bacterial load in a model mouse abscess caused by MRSA persisters in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jun Liu, Jin-Song Hou, Yi-Qun Chang, Li-Jun Peng, Xiao-Yi Zhang, Zhi-Ying Miao, Ping-Hua Sun, Jing Lin, Wei-Min Chen
Summary: Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to combat Pseudomonas aeruginosa resistance. Compound 20p was identified as a potential novel antibacterial synergist candidate for the treatment of P. aeruginosa infections, showing significant antibacterial synergy when combined with approved antibiotics for CF.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yuan -Yuan Wang, Xiao-Yi Zhang, Xiao-Lin Zhong, Yong-Jun Huang, Jing Lin, Wei -Min Chen
Summary: We report a series of 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates designed as dual antibacterial and antibiofilm agents against Pseudomonas aeruginosa. The 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1H)-one-ciprofloxacin conjugate (5e) showed the best minimum inhibitory concentrations and reduced biofilm formation by 78.3%. Additionally, 5e eradicated mature biofilms and killed living bacterial cells within the biofilm. Mechanistic studies revealed that 5e interfered with iron uptake, inhibited motility, and reduced virulence production. These findings highlight the potential of 3-hydroxy-pyridin-4(1H)-ones-ciprofloxacin conjugates for treating biofilm-associated drug-resistant Pseudomonas aeruginosa infections.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jun Liu, Ying Meng, Ming-Han Yang, Xiao-Yi Zhang, Jian-Fu Zhao, Ping-Hua Sun, Wei-Min Chen
Summary: In this study, several 3-hydroxypyridin-4(1H)-one hybrids were designed and synthesized, and their potential as inhibitors of P. aeruginosa biofilm formation was evaluated. The most active compound, 12h, exhibited significant biofilm inhibitory activity. Mechanistic studies revealed that 12h inhibited biofilm formation by suppressing the expression of lasB and pqsA. Furthermore, 12h improved the antibiotic susceptibility of P. aeruginosa and reduced its acute virulence in Vero cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yong-Jun Huang, Xiao-Lin Zhong, Yi-Peng Zang, Ming-Han Yang, Jing Lin, Wei -Min Chen
Summary: The natural prenylated chalcone isobavachalcone (IBC) is effective against Gram-positive bacteria but not Gram-negative bacteria due to the outer membrane barrier. In this study, conjugates of 3-hydroxy-pyridin-4(1H)-ones and IBC were designed and synthesized based on the Trojan horse strategy. The conjugates showed lower MICs and IC50s against Pseudomonas aeruginosa PAO1 and MDR strains compared to IBC, and their antibacterial activity was regulated by the bacterial iron uptake pathway.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Qian-Wen Lin, Jin-Qiang Lu, Ye-Si Huang, Jie-Jiao Liu, Wei-Min Chen, Jing Lin
Summary: A c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@NO) was designed and synthesized as a bifunctional antibiofilm agent. It showed better biofilm inhibition efficiency and could eradicate mature biofilm. It also exhibited good antimicrobial synergism against Pseudomonas aeruginosa and improved the bactericidal efficiency of tobramycin against biofilm-forming bacteria. In combination with tobramycin, A11@NO also improved the survival rate of Caenorhabditis elegans in a hyperbiofilm environment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Wen Hou, Zhen-Ya Wang, Jing Lin, Wei-Min Chen
CELL DEATH DISCOVERY
(2020)
Article
Chemistry, Multidisciplinary
Zi-Qiang Wang, Teng-Fei Xuan, Jun Liu, Wei-Min Chen, Jing Lin