Article
Chemistry, Multidisciplinary
Christian Schuetz, Duy-Khiet Ho, Mostafa Mohamed Hamed, Ahmed Saad Abdelsamie, Teresa Roehrig, Christian Herr, Andreas Martin Kany, Katharina Rox, Stefan Schmelz, Lorenz Siebenbuerger, Marius Wirth, Carsten Boerger, Samir Yahiaoui, Robert Bals, Andrea Scrima, Wulf Blankenfeldt, Justus Constantin Horstmann, Rebekka Christmann, Xabier Murgia, Marcus Koch, Aylin Berwanger, Brigitta Loretz, Anna Katharina Herta Hirsch, Rolf Wolfgang Hartmann, Claus-Michael Lehr, Martin Empting
Summary: A new generation of quorum sensing inhibitors (QSI) is reported to effectively inhibit the virulence of Pseudomonas aeruginosa and enhance antibiotic efficacy, potentially preventing the development of antimicrobial resistance. Additionally, a significant synergistic effect of QSI in combination with tobramycin against P. aeruginosa biofilms is demonstrated, showing promising implications for adjunctive pathoblocker-mediated therapy.
Article
Biochemistry & Molecular Biology
Selene Garcia-Reyes, Miguel Cocotl-Yanez, Martin Paolo Soto-Aceves, Abigail Gonzalez-Valdez, Luis Servin-Gonzalez, Gloria Soberon-Chavez
Summary: This study characterized the PqsE-dependent production of PYO in Pseudomonas aeruginosa ATCC 9027 and found that PqsE promotes the RhlR-dependent production of PYO, although this production is not strictly dependent on PqsE. The interaction between PqsE and RhlR modifies the transcription of genes involved in PYO production, highlighting the variability of the quorum-sensing response among different P. aeruginosa clades and strains.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Vijay K. K. Singh, Marianna Almpani, Kelsey M. M. Wheeler, Laurence G. G. Rahme
Summary: Pseudomonas aeruginosa is a common multidrug-resistant bacterial pathogen that poses a serious threat to critically ill and immunocompromised patients. Intestinal colonization by this pathogen is associated with increased mortality rates. In this study, the role of the three major communication systems in P. aeruginosa was investigated, and it was found that the MvfR system plays a key role in intestinal inflammation while the other systems have relatively minor effects. This study reveals the interrelationships of the quorum sensing systems during infection and provides important insights for developing effective antivirulence strategies.
Article
Chemistry, Medicinal
Fadi Soukarieh, Alaa Mashabi, William Richardson, Eduard Vico Oton, Manuel Romero, Shaun N. Roberston, Scott Grossman, Tomas Sou, Ruiling Liu, Nigel Halliday, Irena Kukavica-Ibrulj, Roger C. Levesque, Christel A. S. Bergstrom, Barrie Kellam, Jonas Emsley, Stephan Heeb, Paul Williams, Michael J. Stocks, Miguel Camara
Summary: This study identified and optimized PqsR antagonists using virtual screening and whole cell assay validation, with compound 61 showing potential as a potent PqsR inhibitor. Compound 61 reduced virulence traits in various strains of P. aeruginosa and enhanced the effect of ciprofloxacin in treating biofilms and infections in Galleria mellonella. These findings suggest compound 61 as a promising lead for developing P. aeruginosa quorum sensing inhibitors for preclinical development.
ACS INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Shekh Sabir, Dittu Suresh, Sujatha Subramoni, Theerthankar Das, Mohan Bhadbhade, David StC. Black, Scott A. Rice, Naresh Kumar
Summary: Synthesized novel DHP analogues can serve as quorum sensing inhibitors for treating P. aeruginosa infections, with one compound effectively inhibiting the pqs system. These inhibitors reduce bacterial aggregation and biofilm formation without affecting planktonic growth.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
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)
Article
Biochemistry & Molecular Biology
Megha Shah, Veronique L. Taylor, Diane Bona, Yvonne Tsao, Sabrina Y. Stanley, Sheila M. Pimentel-Elardo, Matthew McCallum, Joseph Bondy-Denomy, P. Lynne Howell, Justin R. Nodwell, Alan R. Davidson, Trevor F. Moraes, Karen L. Maxwell
Summary: The study identified a new phage anti-activator protein, Aqs1, which inhibits phage infection by suppressing the quorum-sensing master regulator LasR. Aqs1 also inhibits the bacterial type IV pilus assembly ATPase protein PilB, preventing phages from superinfecting host cells. This research highlights the potential of small phage proteins to disrupt key biological pathways and offers insights into the evolutionary dynamics between phages and their hosts.
Article
Microbiology
Zhidong Zhang, Yang Sun, Yuanyang Yi, Xiaoyu Bai, Liying Zhu, Jing Zhu, Meiying Gu, Yanlei Zhu, Ling Jiang
Summary: A strain of Streptomyces with quorum-sensing inhibitory activity was isolated from the Kumutag Desert in Xinjiang, and it effectively inhibited biofilm formation and virulence factor production in bacteria such as Pseudomonas aeruginosa.
Review
Chemistry, Medicinal
Mohammad Anwar Hossain, Nadezhda A. German
Summary: In recent years, modulators of quorum sensing pathways in Pseudomonas aeruginosa have gained attention for their potential therapeutic applications, including enhancing the efficacy of existing therapeutic agents against resistant strains. Additionally, these chemical agents can be utilized in various fields such as developing anticancer therapeutics and artificial biological systems.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Qiaoqiang Li, Shen Mao, Hong Wang, Xinyi Ye
Summary: The survival pressure caused by antibiotics prompts bacteria to develop drug resistance. Quorum sensing is an intercellular communication system that regulates bacterial virulence and biofilm formation. In Pseudomonas aeruginosa, the formation and diffusion of biofilm is closely related to the quorum sensing system. Quorum-sensing inhibitors can reduce bacterial toxicity and enhance sensitivity to antibiotics, making them a popular topic for research and development in anti-infection. This review provides an overview of the Pseudomonas aeruginosa quorum-sensing system and quorum-sensing inhibitors research, which will aid in the future development of novel inhibitors.
Article
Biochemistry & Molecular Biology
Dittu Suresh, Shekh Sabir, Tsz Tin Yu, Daniel Wenholz, Theerthankar Das, David StC. Black, Naresh Kumar
Summary: Rottlerin, a natural product, has the potential to inhibit the quorum sensing system in bacteria. By synthesizing Rottlerin analogues, it was found that certain structures exhibited high quorum sensing inhibitory activity, moderate biofilm inhibitory activity, and reduced pyocyanin production.
Review
Biochemistry & Molecular Biology
Kayeen Vadakkan, Ajit Kumar Ngangbam, Kuppusamy Sathishkumar, Nelson Pynadathu Rumjit, Meena Kochappan Cheruvathur
Summary: Pseudomonas aeruginosa, a competitive and biofilm organism with complex quorum systems, poses a significant threat to the medical industry. Inhibiting quorum sensing could be a potential strategy for treating bacterial infections and developing anti-virulent tools.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Chemistry, Medicinal
Hongrui Ji, Lu Zhao, Kaiwen Lv, Yuzhu Zhang, Haibo Gao, Qianhong Gong, Wengong Yu
Summary: Pseudomonas aeruginosa is an opportunistic pathogen that uses a quorum sensing system to protect itself from antibiotics and environmental stress. A marine fungus, Penicillium sp. JH1, was found to produce a novel quorum sensing inhibitor called citrinin, which can inhibit the production of violacein in Chromobacterium violaceum and three virulence factors in P. aeruginosa. Citrinin can also inhibit biofilm formation and motility of P. aeruginosa, and downregulate the expression of genes associated with quorum sensing.
Article
Multidisciplinary Sciences
Parker Smith, Martin Schuster
Summary: Quorum sensing is a widespread cell density-dependent signaling mechanism in bacteria. This study demonstrates the role of antiactivators in preventing self-sensing in the quorum sensing system of Pseudomonas aeruginosa.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Shouyi Li, Xuetao Gong, Liwen Yin, Xiaolei Pan, Yongxin Jin, Fang Bai, Zhihui Cheng, Un-Hwan Ha, Weihui Wu
Summary: This study reveals a novel regulatory mechanism in Pseudomonas aeruginosa, where CspC protein regulates the quorum-sensing systems by repressing the translation of a negative regulator gene, rsaL, in response to a host-generated metabolite.
Review
Cell Biology
Zoe Markham-Lee, Neil Morgan, Jonas Emsley
Summary: ADAMTS13 is a plasma metalloprotease that cleaves VWF to maintain hemostasis, and its mutations are associated with Thrombotic Thrombocytopenic Purpura. Molecular characterization of ADAMTS13 is important for understanding the mechanisms of TTP.
Article
Biochemistry & Molecular Biology
Valentina Cuzzucoli Crucitti, Aleksandar Ilchev, Jonathan C. Moore, Harriet R. Fowler, Jean-Frederic Dubern, Olutoba Sanni, Xuan Xue, Bethany K. Husband, Adam A. Dundas, Sean Smith, Joni L. Wildman, Vincenzo Taresco, Paul Williams, Morgan R. Alexander, Steven M. Howdle, Ricky D. Wildman, Robert A. Stockman, Derek J. Irvine
Summary: This study utilized the alpha parameter, a molecular descriptor, to design terpene-based polymers resistant to biofilm formation by Pseudomonas aeruginosa. The potential biofilm resistance of terpene-derived monomers was predicted and ranked using the alpha parameter. The monomers from commercially available terpenes were polymerized and confirmed to have biofilm resistance properties. The scaled-up monomers were successfully printed and used to create bio-instructive microparticles. The observations in this study have significant potential to produce bio-resistant coatings, packaging materials, fibers, and medical devices.
Article
Multidisciplinary Sciences
Jean-Frederic Dubern, Andrew L. Hook, Alessandro M. Carabelli, Chien-Yi Chang, Christopher A. Lewis-Lloyd, Jeni C. Luckett, Laurence Burroughs, Adam A. Dundas, David J. Humes, Derek J. Irvine, Morgan R. Alexander, Paul Williams
Summary: Innovative approaches are urgently needed to prevent catheter-associated urinary tract infections (CAUTIs). A newly discovered acrylate copolymer has shown promising resistance against bacterial biofilm formation, swarming, encrustation, and host protein deposition, all of which are major challenges in preventing CAUTIs. The copolymer, poly(tert-butyl cyclohexyl acrylate), combined with poly(2-hydroxy-3-phenoxypropyl acrylate) has demonstrated its potential as a urinary catheter coating by retaining its bioinstructive properties and maintaining resistance against various uropathogens.
Article
Nanoscience & Nanotechnology
Leonardo Contreas, Andrew L. Hook, David A. Winkler, Grazziela Figueredo, Paul Williams, Charles A. Laughton, Morgan R. Alexander, Philip M. Williams
Summary: Bacterial infections are becoming a greater concern due to antimicrobial resistance. The rational design of materials resistant to biofilm formation is a crucial strategy to prevent infections related to medical devices. Machine learning has been used to identify strong associations between bacterial adhesion and the physicochemical properties of polyacrylate libraries. However, the interpretability of nonlinear models is limited, making it challenging to understand the molecular interactions between materials and bacteria.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Analytical
Shaun N. Robertson, Fadi Soukarieh, Thomas M. White, Miguel Camara, Manuel Romero, Rian L. Griffiths
Summary: Previously, metabolites from microbial samples were analyzed using liquid chromatography-mass spectrometry. This study presents a model system for studying the microbial exometabolome by growing biofilms on discs and using liquid extraction surface analysis. The specific surface nature of this approach allows for mimicking biofilm formation and studying the interplay between commonly combined causative agents of infection. The results suggest that certain signal molecules are important markers of infection, and monitoring their levels can aid in determining causative agents in interkingdom infection.
ANALYTICAL CHEMISTRY
(2023)
Article
Biophysics
Heba Khateb, Andrew L. Hook, Stefanie Kern, Julie A. Watts, Sonali Singh, Darryl Jackson, Luisa Marinez-Pomares, Paul Williams, Morgan R. Alexander
Summary: The use of OrbiTrap analyzer with SIMS (3D OrbiSIMS) enables label-free mass spectrometry of Psl, accurately identifying secondary ion peaks specific to the Psl structure. By studying P. aeruginosa biofilm and purified Psl, 17 peaks associated with Psl fragments within the biofilm matrix were confidently identified. Additionally, the neutral loss sequences approach can also identify multiple oligosaccharide fragments without a biological reference sample.
Article
Microbiology
Jean-Frederic Dubern, Nigel Halliday, Miguel Camara, Klaus Winzer, David A. Barrett, Kim R. Hardie, Paul Williams
Summary: Quorum sensing (QS) in Pseudomonas aeruginosa relies on the Las, Rhl, and Pqs systems to regulate the synthesis of AHLs and AQs. While QS is commonly thought to be population density-dependent, this study demonstrates that growth rate and population density independently modulate the accumulation of AHLs and AQs. Different nutrient limitations, temperature, and mutation of key QS genes also affect the production of AHLs and AQs in P. aeruginosa. QS imposes an energetic drain on the bacterium by consuming key substrates and ATP.
Article
Polymer Science
Fadi Soukarieh, Pratik Gurnani, Manuel Romero, Nigel Halliday, Michael Stocks, Cameron Alexander, Miguel Camara
Summary: Antimicrobial resistance is a global threat with a forecasted negative financial impact. Bacteria resistance is further enhanced by the ability to form biofilms, making most treatments ineffective. A study has developed polymers that improve the penetration of inhibitors to enhance biofilm antimicrobial activity.
Article
Immunology
Giulia Giallonardi, Morgana Letizia, Marta Mellini, Emanuela Frangipani, Nigel Halliday, Stephan Heeb, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Paul Williams, Giordano Rampioni
Summary: Pseudomonas aeruginosa is a model pathogen with multiple quorum sensing circuits that control virulence factor production and biofilm formation. The pqs QS system in P. aeruginosa synthesizes AQs including HHQ and PQS, which act as signal molecules. Transcriptomic analyses show that HHQ and PQS influence gene expression through PqsR-dependent and -independent pathways. However, HQNO has no effect on P. aeruginosa transcriptome. Mutation of pqsL in P. aeruginosa leads to autolysis in colony biofilms through the accumulation of HHQ and activation of Pf4 prophage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
See Yoong Wong, Andrew L. Hook, Wil Gardner, Chien-Yi Chang, Ying Mei, Martyn C. Davies, Paul Williams, Morgan R. Alexander, Davide Ballabio, Benjamin W. Muir, David A. Winkler, Paul J. Pigram
Summary: Biofilm formation is a major problem in hospitals, and researching biofilm-resistant materials is critical. Polymer microarrays can efficiently discover new biofilm-resistant polymers. This study investigates bacterial attachment and surface chemistry on a polymer microarray to better understand Pseudomonas aeruginosa biofilm formation. Analyzing the data using linear multivariate analysis and a nonlinear self-organizing map reveals fragment ions associated with bacterial biofilm formation. Considering these insights, a second analysis is conducted that explicitly considers interactions between key fragments. This improved model provides chemical insights for designing materials that prevent pathogen attachment.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Philip Bardelang, Ewan J. Murray, Isobel Blower, Sara Zandomeneghi, Alice Goode, Rohanah Hussain, Divya Kumari, Giuliano Siligardi, Katsuaki Inoue, Jeni Luckett, James Doutch, Jonas Emsley, Weng C. Chan, Philip Hill, Paul Williams, Boyan B. Bonev
Summary: The virulence gene expression in S. aureus is controlled by the agr quorum sensing system, and the AgrB and AgrD proteins play important roles in this process. Through homology modelling and molecular dynamics techniques, the conformations of AgrB and AgrD were characterized and their interaction mechanisms were analyzed. Experimental evidence confirmed the direct interaction between AgrB and AgrD, and the formation of AgrBD complex in vitro. These findings contribute to a better understanding of the mechanisms behind the regulation of virulence gene expression in S. aureus.
FRONTIERS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Macauley J. Green, Ewan J. Murray, Paul Williams, Amir M. Ghaemmaghami, Jonathan W. Aylott, Philip M. Williams
Summary: Under low-shear modeled microgravity conditions, Staphylococcus aureus exhibited a colonization phenotype instead of a pathogenic one, due to reduced production of autoinducing peptide signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Marta Mellini, Morgana Letizia, Lorenzo Caruso, Alessandra Guiducci, Carlo Meneghini, Stephan Heeb, Paul Williams, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Giordano Rampioni
Summary: Quorum sensing allows single cells to synchronize gene expression in bacterial populations, but studies have shown significant cell-to-cell variation in this process, resulting in coexisting subpopulations of active and inactive cells. The molecular mechanisms behind this phenomenon, particularly in the las QS system of Pseudomonas aeruginosa, have not been fully defined.
Article
Hematology
Chan Li, Awital Bar Barroeta, Szu Shen Wong, Hyo Jung Kim, Monika Pathak, Ingrid Dreveny, Joost C. M. Meijers, Jonas Emsley
Summary: The structure of the complex formed between HK and PK apple domains was determined, revealing different conformations and interactions compared to the FXI-HK complex.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Foteini-Nafsika Damaskinaki, Natalie J. Jooss, Eleyna M. Martin, Joanne C. Clark, Mark R. Thomas, Natalie S. Poulter, Jonas Emsley, Barrie Kellam, Steve P. Watson, Alexandre Slater
Summary: This study investigates the binding sites of three high-affinity nanobodies, Nb2, Nb21, and Nb35, on the platelet-signaling receptor GPVI. The researchers found that all three nanobodies can bind to the D1 domain of GPVI and inhibit collagen-induced GPVI signaling. They also identified common target residues, Arg46, Tyr47, and Ala57, on GPVI for these nanobodies. Additionally, the study negates the idea that GPVI dimerization induces a conformational change required for ligand binding.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
