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
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
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)
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
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)
Article
Biochemistry & Molecular Biology
Laurent Gavara, Alice Legru, Federica Verdirosa, Laurent Sevaille, Lionel Nauton, Giuseppina Corsica, Paola Sandra Mercuri, Filomena Sannio, Georges Feller, Remi Coulon, Filomena De Luca, Giulia Cerboni, Silvia Tanfoni, Giulia Chelini, Moreno Galleni, Jean-Denis Docquier, Jean-Francois Hernandez
Summary: Researchers are developing compounds based on the 1,2,4-triazole-3-thione scaffold to target resistance mechanisms in Gram-negative bacteria, with promising potential for broad-spectrum inhibitors. These compounds, particularly those containing a carboxylic group at the 4-position, have shown potent inhibition against VIM-type enzymes. Further exploration is needed to improve outer membrane penetration and efficacy against other carbapenemases.
BIOORGANIC CHEMISTRY
(2021)
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
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)
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
Chemistry, Medicinal
Yue-Juan Zhang, Le Zhai, Yi Wan, Ke-Wu Yang
Summary: A series of triazolylthioacetamides were synthesized and exhibited specific inhibitory activity against IMP-1, potentially enhancing the antibacterial efficacy of cefazolin. Some compounds showed low cytotoxicity in cell assays. These findings indicate that triazolylthioacetamides could serve as effective inhibitors of metallo-beta-lactamases.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
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
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
Biochemistry & Molecular Biology
Okke Melse, Samuel Sutiono, Magdalena Haslbeck, Gerhard Schenk, Iris Antes, Volker Sieber
Summary: In this study, the functionality and activity relationships of FeS-dependent dehydratases were investigated in vitro and in silico, resulting in a proposed classification based on evolutionary relationships and substrate profiles. Key positions affecting specificity were identified through simulations and analyses, which were experimentally verified. This research provides guidance for further development of this important biocatalyst for industrial applications.
Article
Chemistry, Multidisciplinary
Tenuun Bayaraa, Jose Gaete, Samuel Sutiono, Julia Kurz, Thierry Lonhienne, Jeffrey R. Harmer, Paul V. Bernhardt, Volker Sieber, Luke Guddat, Gerhard Schenk
Summary: There is an urgent need worldwide to develop novel therapeutics to combat antibiotic-resistant superbugs. Enzymes in the branched-chain amino acid (BCAA) biosynthesis pathway are attractive targets for the development of new antimicrobial drugs. Recent research has focused on dihydroxy-acid dehydratase (DHAD), the third enzyme in the BCAA biosynthesis pathway, which has shown catalytic activity in cell-free enzyme cascades. In this study, researchers characterized DHADs from two bacterial human pathogens and identified potential inhibitors that could be used as starting points for the development of new antimicrobial chemotherapeutics.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Marion Ringel, Nicole Dimos, Stephanie Himpich, Martina Haack, Claudia Huber, Wolfgang Eisenreich, Gerhard Schenk, Bernhard Loll, Thomas Brueck
Summary: This study identified two novel terpene synthases from the wood rotting fungus Coniophora puteana, which can catalyze the production of a potentially new bioactive compound, (+)-delta-cadinol. Mutagenesis studies revealed that the catalytic cycle of these enzymes may involve different conformational changes, suggesting a more complex role of tertiary structure elements in terpene synthase reactions. These findings may contribute to the sustainable production of bioactive compounds and serve as a model system for further mechanistic studies of terpenoid catalysis.
MICROBIAL CELL FACTORIES
(2022)
Article
Pharmacology & Pharmacy
Ahmed O. Shalash, Armira Azuar, Harrison Y. R. Madge, Naphak Modhiran, Alberto A. Amarilla, Benjamin Liang, Alexander A. Khromykh, Waleed M. Hussein, Keith J. Chappell, Daniel Watterson, Paul R. Young, Mariusz Skwarczynski, Istvan Toth
Summary: The SARS-CoV-2 virus has caused a global crisis with billions of infections and millions of deaths. Current DNA and mRNA vaccines have shown decreased efficacy over time, especially the Pfizer BNT162 vaccine. Variant strains have further reduced vaccine effectiveness. Peptide vaccines offer an alternative solution with greater stability and flexibility to target emerging strains.
Article
Biotechnology & Applied Microbiology
Michael Paper, Matthias Glemser, Martina Haack, Jan Lorenzen, Norbert Mehlmer, Tobias Fuchs, Gerhard Schenk, Daniel Garbe, Dirk Weuster-Botz, Wolfgang Eisenreich, Michael Lakatos, Thomas B. Brueck
Summary: This study demonstrates that the marine chlorophyte Picochlorum sp. can efficiently grow under green light illumination and produce unknown pigments. Green light illumination can enhance biomass production and trigger the formation of new metabolites.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Armira Azuar, Harrison Y. R. Madge, Jennifer C. Boer, Jazmina L. Gonzalez Cruz, Jingwen Wang, Zeinab G. Khalil, Cyril Deceneux, Georgia Goodchild, Jieru Yang, Prashamsa Koirala, Waleed M. Hussein, Robert J. Capon, Magdalena Plebanski, Istvan Toth, Mariusz Skwarczynski
Summary: Adjuvants and delivery systems are crucial for enhancing immunogenicity of peptide-based vaccines. A poly(hydrophobic amino acids) delivery system self-assembles into nanoparticles with self-adjuvating ability, which can be further integrated into liposomes to boost immunological responses. Anchoring polyleucine-based conjugates to cationic liposomes induces significant mucosal and systemic immunity in mice.
Review
Immunology
Jingyi Fan, Shengbin Jin, Lachlan Gilmartin, Istvan Toth, Waleed M. Hussein, Rachel J. Stephenson
Summary: Vaccines are crucial in fighting infectious diseases, and the development of safe and effective vaccines is a challenge. Immune stimulants, or adjuvants, play a vital role in vaccine development by enhancing and prolonging immune responses. However, the potential for adverse effects must be carefully managed. Understanding the efficacy and safety mechanisms of adjuvants is essential for vaccine administration.
Article
Biochemistry & Molecular Biology
Liam A. Wilson, Marcelo M. Pedroso, Rosely A. Peralta, Lawrence R. Gahan, Gerhard Schenk
Summary: Biomimetics have potential applications in biotechnology and medicine, and are often used as benchmarks for studying more complex biological systems. However, the catalytic efficiencies of synthetic systems are often inferior to their biological counterparts due to their smaller size and lower complexity. Nonetheless, artificial catalysts inspired by biology have been developed to mimic various chemical transformations. In this article, we discuss biomimetics of the metallohydrolase purple acid phosphatase (PAP) and the seminal contributions of Prof. Ademir Neves and his group in designing ligands that mimic the active site of PAP.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Luel M. O. Costa, Iago S. Reis, Christiane Fernandes, Marcelo M. Marques, Jackson A. L. C. Resende, Elizabeth H. Krenske, Gerhard Schenk, Lawrence R. Gahan, Adolfo Horn Jr
Summary: We synthesized a new asymmetric heptadentate ligand based on the 1,3-diaminopropan-2-ol back-bone. The ligand contains two amide and two pyridine groups attached to the core. Reaction with Zn(ClO4)2.6H2O resulted in the formation of a dinuclear complex. The complex showed pH-dependent phosphatase activity with the highest activity at pH 9.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Immunology
Jieru Yang, Jennifer C. Boer, Mattaka Khongkow, Sarunya Phunpee, Zeinab G. Khalil, Sahra Bashiri, Cyril Deceneux, Georgia Goodchild, Waleed M. Hussein, Robert J. Capon, Uracha Ruktanonchai, Magdalena Plebanski, Istvan Toth, Mariusz Skwarczynski
Summary: Intranasal vaccine administration has advantages in mass immunization. A new liposomal system using lipidated chitosan derivative (OTMC) showed promising results in stimulating high systemic antibody titers against group A Streptococcus (GAS) in mice. OTMC was more effective than the traditional trimethyl chitosan formulation and could enhance the immune responses of the vaccine without the need for a liposome delivery system. Importantly, OTMC also stimulated cytokine production by dendritic cells, indicating its potential for mucosal vaccine development.
Article
Agriculture, Multidisciplinary
Yan Cheng, Thierry Lonhienne, Mario D. Garcia, Craig M. Williams, Gerard Schenk, Luke W. Guddat
Summary: Amidosulfuron (AS), a commercial sulfonylurea herbicide, effectively targets dicot broadleaf weeds by inhibiting acetohydroxyacid synthase (AHAS) in the plants. The crystal structure analysis shows that AS lacks a second aromatic ring compared to other AHAS-inhibiting herbicides, but still exhibits potent herbicidal activity through accumulative inhibition. This study highlights the importance of accumulative inhibition in designing effective herbicides targeting plant AHAS.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Physical
Vindi M. Jayasinghe-Arachchige, Leonardo F. Serafim, Qiaoyu Hu, Cihan Ozen, Sreerag N. Moorkkannur, Gerhard Schenk, Rajeev Prabhakar
Summary: The hydrolytic activities of hetero- and homobinuclear metallovariants of an asymmetric or symmetric ligand with Fe-III-Zn-II, Zn-II-Zn-II, and Cu-II-Cu-II cores are studied using DFT calculations. The effects of different nucleophiles, coordination numbers, para substituents of the linker, and an external electric field on the energetics of these reactions are computed. The study highlights the influence of critical chemical factors on phosphoester hydrolysis and provides insights for designing versatile metal complexes for various reactions and applications.
Article
Pharmacology & Pharmacy
Farrhana Z. Z. Firdaus, Stacey Bartlett, Waleed M. M. Hussein, Lantian Lu, Quentin Wright, Wenbin Huang, Ummey J. J. Nahar, Jieru Yang, Mattaka Khongkow, Margaret Veitch, Prashamsa Koirala, Uracha R. R. Ruktanonchai, Michael J. J. Monteiro, Jazmina L. Gonzalez L. Cruz, Rachel J. J. Stephenson, James W. W. Wells, Istvan Toth, Mariusz Skwarczynski
Summary: Human papilloma virus (HPV) is responsible for all cases of cervical cancer. Peptide-based vaccines, such as 8Qm conjugated to polyleucine, show promise as a therapeutic option with fewer side effects compared to chemotherapy and surgery. Liposomes incorporating the 8Qm conjugate demonstrated efficacy in tumor eradication, while the introduction of DC-targeting moieties did not significantly improve vaccine efficacy.
Article
Microbiology
Karen Rodriguez, Marcelo Pedroso, Audrey Harris, Shivani Garg, Damian Hine, Michael Kopke, Gerhard Schenk, Esteban Marcellin
Summary: The challenge of limiting global warming to below 1.5°C requires immediate implementation of new technologies and practices in all industries. The aviation industry, which accounts for 2% of human-induced CO2 emissions and 12% of all transport emissions, has faced difficulties in decarbonizing due to its heavy reliance on high-density liquid fuels. The use of sustainable aviation fuels, derived from first-generation agricultural feedstocks, also creates a trade-off between biomass for food and energy generation. Developing electric aircraft has also presented challenges in decarbonizing aviation. Gas fermentation technologies, utilizing greenhouse gases from food production and waste, offer a feasible alternative for replacing fossil fuels in aviation fuel production, particularly in Australia where there are abundant feedstock resources.
MICROBIOLOGY AUSTRALIA
(2023)
Article
Chemistry, Multidisciplinary
Li Chen Cheah, Lian Liu, Manuel R. Plan, Bingyin Peng, Zeyu Lu, Gerhard Schenk, Claudia E. Vickers, Frank Sainsbury
Summary: Enzyme spatial organization is evolved to facilitate biocatalysis and regulate promiscuous enzymes. Artificial spatial organization can be used to control the specificity of bioengineered metabolic pathways. Co-localization and spatial organization of a promiscuous terpene synthase with the preceding enzyme enhances product production and modulates the ratio of end products.
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)
