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
Chemistry, Multidisciplinary
Katarzyna Palica, Manuela Voracova, Susann Skagseth, Anna Andersson Rasmussen, Lisa Allander, Madlen Hubert, Linus Sandegren, Hanna-Kirstirep Schroder Leiros, Hanna Andersson, Mate Erdelyi
Summary: Infectious diseases remain a major concern for public health in the 21st century, and the development of antimicrobial resistance by microbes is a significant problem. The study found that phosphonamidate compounds have the potential to become a new generation of antibiotic therapeutics to combat metallo-beta-lactamase-resistant bacteria.
Article
Biochemistry & Molecular Biology
Marco J. J. Rotter, Sabrina Zentgraf, Lilia Weizel, Denia Frank, Luisa D. Burgers, Steffen Brunst, Robert Fuerst, Anna Proschak, Thomas A. Wichelhaus, Ewgenij Proschak
Summary: Metallo beta lactamases (MBLs) have become a major problem in treating multidrug-resistant Gram-negative pathogens due to their ability to resist a broad range of drugs and lack of effective inhibitors. In this study, we designed catechol-containing MBL inhibitors that mimic bacterial siderophores, which are actively taken up by bacteria through their iron acquisition system. The most potent catechol-containing MBL inhibitor demonstrated binding to Fe3+ ions and restored the effectiveness of imipenem in NDM-1-expressing K. pneumoniae without affecting healthy cells. These siderophore-containing MBL inhibitors could be a promising strategy to combat MBL-mediated resistance to beta lactam antibiotics.
Article
Chemistry, Multidisciplinary
Radhika Mehta, Dann D. Rivera, David J. Reilley, Dominique Tan, Pei W. Thomas, Abigail Hinojosa, Alesha C. Stewart, Zishuo Cheng, Caitlyn A. Thomas, Michael W. Crowder, Anastassia N. Alexandrova, Walter Fast, Emily L. Que
Summary: The development of a fluorescent probe that reports on the metalation state of NDM within Escherichia coli provides a novel tool to study metal ion sequestration in host-pathogen interactions. The probe selectively coordinates the dizinc metal cluster of NDM and offers a way to monitor the enzyme's response to metal ions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Nicola Wade, Kamaleddin H. M. E. Tehrani, Nora C. Bruchle, Matthijs J. van Haren, Vida Mashayekhi, Nathaniel I. Martin
Summary: This study elucidated the inhibitory mechanisms of a panel of structurally distinct MBL inhibitors, finding clear differences in terms of IC50 value, metal binding ability, and synergy with meropenem. The capacity of an inhibitor to strongly chelate zinc does not explicitly determine potent MBL inhibition and synergy with meropenem.
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, Medicinal
Zainab Bibi, Irfa Asghar, Naeem Mahmood Ashraf, Iftikhar Zeb, Umer Rashid, Arslan Hamid, Maria Kanwal Ali, Ashraf Atef Hatamleh, Munirah Abdullah Al-Dosary, Raza Ahmad, Muhammad Ali
Summary: This study utilized virtual screening and molecular dynamics simulations to explore phytochemicals as inhibitors of New Delhi Metallo-beta-lactamase (NDM-1). Three potential inhibitors were identified based on their docking scores, RMSD values, and other critical parameters. These findings could contribute to addressing antibiotic resistance.
Article
Infectious Diseases
Cecile Emeraud, Sandrine Bernabeu, Laurent Dortet
Summary: Combining aztreonam with imipenem-relebactam and meropenem-vaborbactam may be useful options to treat aztreonam-non-susceptible MBL-producing Gram-negative strains.
Article
Chemistry, Multidisciplinary
Lingyan Kong, Yilin Zhang, Liwen Yang, Yong Yan, Min Cheng, Xuejun Wang, Le Zhai, Kewu Yang
Summary: The metallo-beta-lactamases (M beta Ls) produced by pathogens pose a challenge to the treatment of bacterial infections worldwide. Oxazolethioacetamides were designed and synthesized as potential M beta Ls inhibitors. Most compounds showed inhibitory activity against M beta L L1, with IC50 values ranging from 0.19 to 0.38 mu M. The fluorine substituted compounds also inhibited VIM-2 with IC50 values ranging from 2.1 to 6.8 mu M. Molecular docking revealed the importance of electron withdrawing groups in the interaction between oxazolethioacetamides and M beta Ls.
Article
Chemistry, Medicinal
Alistair J. M. Farley, Yuri Ermolovich, Karina Calvopina, Patrick Rabe, Tharindi Panduwawala, Jurgen Brem, Fredrik Bjorkling, Christopher J. Schofield
Summary: N-sulfamoylpyrrole-2-carboxylates (NSPCs) show promise as efficient MBL inhibitors, restoring antibiotic efficacy in clinically relevant bacteria. Further optimization is needed for clinical development, but the results are encouraging.
ACS INFECTIOUS DISEASES
(2021)
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
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)
Review
Biochemistry & Molecular Biology
Yongqiang Yang, Yu-Hang Yan, Christopher J. Schofield, Alan McNally, Zhiyong Zong, Guo-Bo Li
Summary: Resistance to beta-lactam antibiotics is a growing concern due to the spread of serine-beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), which efficiently break down beta-lactam antibiotics. While inhibitors for SBLs have been successful in clinical use, there are currently no inhibitors for MBLs. MBLs are particularly worrisome as they can break down most beta-lactam antibiotics and are rapidly disseminating across bacterial species worldwide.
TRENDS IN MICROBIOLOGY
(2023)
Article
Chemistry, Medicinal
Philip Hinchliffe, Diego M. Moreno, Maria-Agustina Rossi, Maria F. Mojica, Veronica Martinez, Valentina Villamil, Brad Spellberg, George L. Drusano, Claudia Banchio, Graciela Mahler, Robert A. Bonomo, Alejandro J. Vila, James Spencer
Summary: The study demonstrates that 2-mercaptomethyl thiazolidines (MMTZs) inhibit metallo-beta-lactamases (MBLs) from different subclasses, enhancing the efficacy of beta-lactam antibiotics against resistant Gram-negative bacteria. The inhibition involves direct interaction of MMTZ thiol with the zinc centers of MBLs, and the stereochemistry at chiral centers plays a critical role in the potency of the inhibitors. Computational studies suggest that MMTZs can inhibit all MBL classes by maintaining conserved binding modes through different routes.
ACS INFECTIOUS DISEASES
(2021)
Article
Chemistry, Medicinal
Nichole K. Stewart, Marta Toth, Anastasiya Stasyuk, Mijoon Lee, Clyde A. Smith, Sergei B. Vakulenko
Summary: Avibactam is a potent irreversible mechanism-based inhibitor of class A and C beta-lactamases, with variable activity against some class D enzymes from Gram-negative bacteria. The interaction of avibactam with recently discovered class D beta-lactamases from Gram-positive bacteria has not been studied. X-ray crystallographic studies demonstrate the rapid formation of a stable CDD-1-avibactam acyl-enzyme complex and differences in anchoring of the inhibitor by class D enzymes from Gram-positive and Gram-negative bacteria.
ACS INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Aasmund Fostervold, Marit A. K. Hetland, Ragna Bakksjo, Eva Bernhoff, Kathryn E. Holt, Orjan Samuelsen, Gunnar Skov Simonsen, Arnfinn Sundsfjord, Kelly L. Wyres, Iren Hoyland Lohr
Summary: The study used nationwide surveillance data to examine longitudinal changes in Klebsiella pneumoniae isolates in Norway, focusing on ESBL-producing strains. The results revealed a diverse ESBL population dominated by specific clonal groups carrying bla(CTX-M-15), indicating convergence of virulence and resistance determinants. Klebsiella variicola was found to be a frequent cause of infection but rarely carried ESBLs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Christopher Frohlich, Vidar Sorum, Nobuhiko Tokuriki, Pal Jarle Johnsen, Orjan Samuelsen
Summary: This study investigated the impact of cefiderocol on resistance development and the evolution of beta-lactamases from different Ambler classes. The expression of bla(KPC-2), bla(CMY-2), bla(CTX-M-15), and bla(NDM-1) significantly reduced cefiderocol susceptibility, while mutations in these enzymes further increased cefiderocol resistance. Resistance development also led to collateral changes in sensitivity to other beta-lactam drugs and functional trade-offs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Aleksandra Jakovljev, Jan Egil Afset, Kjersti Haugum, Harald Otto Steinum, Torunn Gresdal Ronning, Orjan Samuelsen, Christina Gabrielsen As
Summary: This study characterized the phenotype and molecular basis of thymine auxotrophy in E. coli isolates from a patient with recurrent bloodstream infection. The isolates showed resistance to TMP-SMX and growth defects. Genomic analysis identified gene mutations associated with resistance. This highlights the risk of resistance development and the challenges in detecting growth-deficient subpopulations in chronic infections.
Article
Multidisciplinary Sciences
Susannah von Hofsten, Marianne Hagensen Paulsen, Synnove Norvoll Magnussen, Dominik Ausbacher, Mathias Kranz, Annette Bayer, Morten B. Strom, Gerd Berge
Summary: Bioprospecting contributes to the discovery of new molecules with anticancer properties. In this study, a new natural product mimic called MPM-1 was found to rapidly kill cancer cells and induce the release of DAMPs, suggesting its potential as a novel anticancer compound.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Manuel K. Langer, Ataur Rahman, Hymonti Dey, Trude Anderssen, Hans -Matti Blencke, Tor Haug, Klara Stensvag, Morten B. Strom, Annette Bayer
Summary: Mimics of antimicrobial peptides (AMPs) have been studied. Heterocyclic scaffolds have a strong influence on the haemolytic activity of compounds. The hydantoin scaffold is identified as a promising template for drug lead development. Among the studied hydantoin derivatives, three lead structures, 2dA, 6cG, and 6dG, show very promising broad-spectrum antimicrobial activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Materials Science, Biomaterials
Lisa Myrseth Hemmingsen, Barbara Giordani, Marianne H. Paulsen, Zeljka Vanic, Goril Eide Flaten, Beatrice Vitali, Purusotam Basnet, Annette Bayer, Morten B. Strom, Natasa Skalko-Basnet
Summary: The eradication of bacteria in biofilms is a major challenge in treating chronic wounds. Antimicrobial peptides and their mimics are potential options, but their clinical use is limited. A study explored the use of a synthetic mimic of an antimicrobial peptide incorporated into liposomes to improve its anti-biofilm effect and anti-inflammatory activity. The results showed that the liposomes effectively eradicated biofilms and reduced inflammation, making them a promising therapeutic option for bacteria-infected chronic wounds.
BIOMATERIALS ADVANCES
(2023)
Article
Multidisciplinary Sciences
Sergio Arredondo-Alonso, George Blundell-Hunter, Zuyi Fu, Rebecca A. Gladstone, Alfred Fillol-Salom, Jessica Loraine, Elaine Cloutman-Green, Pal J. Johnsen, Orjan Samuelsen, Anna K. Poentinen, Francois Cleon, Susana Chavez-Bueno, Miguel A. De la Cruz, Miguel A. Ares, Manivanh Vongsouvath, Agnieszka Chmielarczyk, Carolyne Horner, Nigel Klein, Alan McNally, Joice N. Reis, Jose R. Penades, Nicholas R. Thomson, Jukka Corander, Peter W. Taylor, Alex J. McCarthy
Summary: Escherichia coli is a leading cause of invasive bacterial infections in humans. The study reveals the distribution, evolution, and functions of the K1 capsule, a potent capsule type, in E. coli. The findings emphasize the importance of assessing virulence factors in population levels to predict and control bacterial infections.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Susannah von Hofsten, Manuel K. Langer, Katja Korelin, Synnove Magnussen, Dominik Ausbacher, Trude Anderssen, Tuula Salo, Morten B. Strom, Annette Bayer, Ahmed Al-Samadi, Gerd Berge
Summary: This study explores the anticancer activity of a panel of novel compounds (marine product mimics, MPMs) against head and neck squamous cell carcinoma (HNSCC) cell lines. The results indicate that these novel MPMs are more potent than the previously reported MPM-1 and can activate the integrated stress response associated with immunogenic cell death. Cell surface expression of calreticulin and release of HMGB1 and ATP, hallmarks of immunogenic cell death, were also demonstrated. The MPMs show potential as interesting candidates for future HNSCC cancer therapies.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Microbiology
Niclas Raffelsberger, Dorota Julia Buczek, Kristian Svendsen, Lars Smabrekke, Anna Kaarina H. Pontinen, Iren Lohr, Lotte Leonore Eivindsdatter Andreassen, Gunnar Skov Simonsen, Arnfinn Sundsfjord, Orjan Norwegian E Coli ESBL Study Grp, Kirsten Gravningen, Orjan Samuelsen
Summary: The global prevalence of infections caused by ESBL-E is increasing, especially community-onset cases. However, there is limited knowledge about the population structure and risk factors for carriage in the community. This study provides insights into the prevalence and population structure of ESBL-E in a general adult population, identifying travel to Asia as a major risk factor for carriage. The genetic diversity of carriage isolates suggests frequent acquisition of ESBL genes, while clinical isolates are more clone dependent and associated with higher antibiotic resistance. These findings have important implications for identifying high-risk patients and preventing the spread of resistant bacteria.
Article
Microbiology
Greta Petazzoni, Greta Bellinzona, Cristina Merla, Marta Corbella, Vincenzina Monzillo, Orjan Samuelsen, Jukka Corander, Davide Sassera, Stefano Gaiarsa, Patrizia Cambieri
Summary: This study provides a detailed investigation of a multidrug-resistant Acinetobacter baumannii outbreak that occurred at a hospital in Italy during the COVID-19 pandemic. The outbreak strains were found to be resistant to carbapenems due to the presence of the carbapenemase gene bla(OXA-23). All strains also carried determinants for biofilm formation. The outbreak was caused by two endemic clones of A. baumannii.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Oskar Ljungquist, Bjorg Haldorsen, Anna Kaarina Pontinen, Jessin Janice, Ellen Haldis Josefsen, Petter Elstrom, Oliver Kacelnik, Arnfinn The Norwegian Study Grp on CPE, Arnfinn Sundsfjord, Orjan Samuelsen
Summary: The incidence of Carbapenemase-producing Enterobacterales (CPE) infection almost doubled between 2015 and 2021, and it was associated with foreign travel and genomic diversity. Continued screening and monitoring are essential to limit further transmission and outbreaks.
Article
Infectious Diseases
Paul Christoffer Lindemann, Torunn Pedersen, Dorthea Hagen Oma, Jessin Janice, Fredrik Grovan, Ghantous Milad Chedid, Liv Jorunn Hafne, Ellen H. Josefsen, Oliver Kacelnik, Arnfinn Sundsfjord, Orjan Samuelsen
Summary: Infections with OXA-244-carbapenemase-producing Escherichia coli ST38 have increased in Europe. This study reports a hospital-associated outbreak of OXA-244-producing E. coli ST38 in Western Norway in 2020. The outbreak occurred over 5 months, involved 12 cases, and the transmission chain was unclear. Outbreak control measures were implemented and no further cases were identified in 2021.
Article
Genetics & Heredity
Sergio Arredondo-Alonso, Rebecca A. Gladstone, Anna K. Pontinen, Joao A. Gama, Anita C. Schurch, Val F. Lanza, Pal Jarle Johnsen, Orjan Samuelsen, Gerry Tonkin-Hill, Jukka Corander
Summary: Extrachromosomal elements of bacterial cells, such as plasmids, play a crucial role in evolution and adaptation. However, the classification of plasmids is still limited, which motivated the development of an efficient approach called mge-cluster that can recognize novel plasmid types and classify them into previously identified groups. This approach offers faster runtime, moderate memory usage, and an intuitive visualization, classification, and clustering scheme within a single framework. By analyzing a population-wide plasmid data set from Escherichia coli, the study highlights the prevalence of the colistin resistance gene and describes plasmid transmission in a hospital environment.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Article
Materials Science, Biomaterials
Alexandra Sousa, Vegard Boroy, Agnethe Baeverud, Kjersti Julin, Annette Bayer, Morten Strom, Mona Johannessen, Natasa Skalko-Basnet, Sybil Obuobi
Summary: Nucleic acid-based materials have great potential for antimicrobial drug delivery. This study focuses on the stability and antibacterial properties of micellar nanocarriers derived from amphiphilic DNA strands against bacterial biofilms. By using a cationic amphiphilic antibiotic, the stability of the micelles is enhanced, their antibacterial activity remains intact, and they can penetrate bacterial biofilms and impact their metabolic activity. The PMB micelles are also highly safe and biocompatible, making them suitable for application against P. aeruginosa biofilm-colonized skin wounds.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Microbiology
Supathep Tansirichaiya, Richard N. Goodman, Xinyu Guo, Issra Bulgasim, Orjan Samuelsen, Mohammed Al-Haroni, Adam P. Roberts
Summary: In this study, the researchers aimed to capture mobile genetic elements (MGEs) in clinical Enterobacteriaceae using the pBACpAK entrapment vector. They successfully captured several insertion sequence (IS) elements and novel transposons. By analyzing the transposition activity within the MGE-free recipient, they gained insights into the interaction and evolution of multidrug resistance-conferring MGEs following conjugation. This study provides a platform for studying the factors affecting intracellular transposition and MGE formation in clinically relevant Enterobacteriaceae.
MICROBIOLOGY SPECTRUM
(2022)
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)