Article
Chemistry, Applied
Meng-Yang Chang, Kuan-Ting Chen
Summary: This paper presents a high-yield and facile method for the synthesis of sulfonyl 2-aroylbenzofurans under mild conditions with water as the only byproduct. Various metal triflate-promoted reactions were investigated for efficient annulation reaction.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Tianzhi Wen, Jian Chen, Wenqian Zhang, Jiyan Pang
Summary: In this study, a series of small-molecule degraders were designed and synthesized based on a known alpha-synuclein aggregation inhibitor sery384. Compound 5 exhibited significant degradation effect on alpha-synuclein aggregates in a time- and dose-dependent manner in vitro.
Article
Chemistry, Medicinal
Biao Xu, Zhi-Peng Wang, Qingwang Liu, Xiaohong Yang, Xuemin Li, Ding Huang, Yanfei Qiu, Kin Yip Tam, Shao-Lin Zhang, Yun He
Summary: This study reported a series of novel dichloroacetophenones as potent PDKs inhibitors, with compound 6u showing significant anti-proliferative effects on various cancer cells. In mouse models, 6u demonstrated potent antitumor activity without negative impact on body weight. The compound was also found to induce cancer cell apoptosis, arrest cell cycle progression, inhibit cell migration, and alter glucose metabolic pathways in cancer cells, showing potential as a modulator for reprogramming glycolysis in cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Agronomy
Aigui Zhang, Jian Yang, Ke Tao, Taiping Hou, Hong Jin
Summary: Novel aromatic carboxamides without a pyrazol group have potential as a class of SDHIs, and the strategy of replacing the pyrazol group with another aryl in the 'core' moiety might offer an alternative option in discovery of SDHI fungicides.
PEST MANAGEMENT SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alberto Cornejo, Julio Caballero, Mario Simirgiotis, Vanessa Torres, Luisa Sanchez, Nicolas Diaz, Marcela Guimaraes, Marcos Hernandez, Carlos Areche, Sergio Alfaro, Leonardo Caballero, Francisco Melo
Summary: The study found that compounds 1 and 1a inhibit beta-aggregation of alpha-synuclein, while 1b does not. Additionally, the interaction between compound 1 and alpha-synuclein affects the morphology of aggregates, and prevents their impact on neurite outgrowth in nerve cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Meiyan Fan, Wei Yang, Lin Liu, Zhiyun Peng, Yan He, Guangcheng Wang
Summary: In order to develop novel alpha-glucosidase inhibitors, a series of chromone-based phenylhydrazone and benzoylhydrazone derivatives were designed, synthesized, and evaluated for their inhibitory effects on alpha-glucosidase. The compounds showed varying degrees of inhibitory activity, with compound 5c being the most potent inhibitor. Mechanistic studies were conducted to elucidate the inhibitory mechanism of compound 5c on alpha-glucosidase. In addition, in vivo tests showed that compound 5c could suppress the rise of blood glucose levels after sucrose loading in mice, and cytotoxicity assays indicated low cytotoxicity of compound 5c.
BIOORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Liduo Yue, Yanbei Ren, Qingxi Yue, Zhou Ding, Kai Wang, Tiansheng Zheng, Guojie Chen, Xiangyun Chen, Ming Li, Lihong Fan
Summary: The study demonstrates that alpha-lipoic acid promotes apoptosis and exerts its antitumor activity against lung cancer by regulating mitochondrial energy metabolism enzyme-related antioxidative stress system. Downregulating the NRF2 antioxidant system is an important mechanism for LA to promote apoptosis.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Immunology
Lucia Lapazio, Monika Braun, Kaj Grandien
Summary: The activation of both CD8 and CD4 T cells is essential for a strong and long-lasting T cell immune response. The study shows that using antigen sequences fused to sequences derived from the H2-M and H2-O proteins can enhance CD4 T-cell activation, potentially improving the efficiency of mRNA- or DNA-based vaccines.
Article
Chemistry, Multidisciplinary
Somaye Karimian, Mohsen Shekouhy, Somayeh Pirhadi, Aida Iraji, Mahshid Attarroshan, Najmeh Edraki, Mehdi Khoshneviszadeh
Summary: In this study, a series of benzimidazole/1,3,5-triazine-2,4-diamine hybrid derivatives were designed and synthesized for the treatment of Alzheimer's disease. The compounds showed inhibitory activity against AChE, BuChE, and BACE1, and interacted with the active sites of AChE and BuChE. In silico analysis of the compounds' ADMET profiles indicated drug-like properties.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Suksamran Chaidam, Natthiya Saehlim, Anan Athipornchai, Uthaiwan Sirion, Rungnapha Saeeng
Summary: A novel series of 1,6-bis-triazole-benzyl-alpha-glucoside derivatives were designed, synthesized, and evaluated for their inhibitory activity against alpha-glucosidase, showing potent inhibitory effects. The ester and menthol moiety were found to be crucial for the activity. Molecular docking models of potent compounds confirmed their good binding energy and interactions with amino acid residues around the enzyme's active site.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Hui Li, Chen Cheng, Shanshan Shi, Yan Wu, Yongfeng Gao, Zhihao Liu, Mingjian Liu, Zhaodong Li, Lijian Huo, Xiapyan Pan, Shuwen Liu, Gaopeng Song
Summary: In this study, UA-18 and its optimized analog UA-30 were identified as novel SARS-CoV-2 fusion inhibitors. The lead compound UA-30 exhibited potent antiviral activity against infectious SARS-CoV-2 and its variants. The mechanism of action of UA-30 involves stabilizing the prefusion state of the SARS-CoV-2 S protein.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Efe Dogukan Dincel, Gozde Hasbal-Celikok, Tugba Yilmaz-Ozden, Nuray Ulusoy-Guzeldemirci
Summary: The newly synthesized imidazo[2,1-b]thiazole derivatives show potential as a novel class of alpha-glucosidase inhibitors for the treatment of type 2 diabetes mellitus. In both in vitro and in vivo experiments, these compounds exhibited significantly higher activity compared to the existing drug Acarbose.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Review
Chemistry, Medicinal
Emilie Anduran, Ludwig L. Dubois, Philippe Lambin, Jean-Yves Winum
Summary: The hypoxic tumor microenvironment presents a persistent challenge in solid tumor treatment. Efforts have been made to develop hypoxia-activated prodrugs (HAPs) of chemotherapeutic compounds to treat hypoxic tumors, but no HAP anti-cancer agent has been commercialized due to the lack of patient stratification based on reliable biomarkers predictive of a positive response to hypoxia-targeted therapy.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Article
Crystallography
Yassine Aimene, Romain Eychenne, Frederic Rodriguez, Sonia Mallet-Ladeira, Nathalie Saffon-Merceron, Jean-Yves Winum, Alessio Nocentini, Claudiu T. Supuran, Eric Benoist, Achour Seridi
Summary: In this work, two classes of Carbonic Anhydrase inhibitors, sulfonamide and coumarin derivatives, were synthesized and evaluated for their inhibitory activity against hCA isoforms. The compounds showed high selectivity and potential anti-cancer properties, with coumarin derivatives demonstrating strong inhibition against tumor-associated isoforms. Molecular docking calculations were performed to rationalize the results and investigate the inhibition profiles at the tumor-associated CA active site.
Article
Chemistry, Medicinal
Chiraz Ismail, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum, Rafik Gharbi
Summary: A series of novel N-triazole-benzene sulfonamides-1,5-benzodiazepines were designed and synthesized through copper-catalyzed click chemistry, with one compound showing high inhibitory activity against various isoforms of human carbonic anhydrase.
ARCHIV DER PHARMAZIE
(2022)
Article
Chemistry, Organic
Amina Merabti, Maxime Roger, Christophe Nguyen, Alessio Nocentini, Philippe Gerbier, Sebastien Richeter, Magali Gary-Bobo, Claudiu T. Supuran, Sebastien Clement, Jean-Yves Winum
Summary: This study describes the synthesis, characterization and optical properties study of innovative tetrafunctionalized zinc(II) porphyrins with carbonic anhydrase (CA) inhibitors in sulfonamide and coumarin series. The compound showed selective inhibition against tumor-associated hCA IX and hCA XII, with efficient photosensitizing properties for cancer cells death under light irradiation, making it a potential candidate for photodynamic therapy.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Microbiology
Jorge A. de la Garza-Garcia, Safia Ouahrani-Bettache, Sebastien Lyonnais, Erika Ornelas-Eusebio, Luca Freddi, Sascha Al Dahouk, Alessandra Occhialini, Stephan Koehler
Summary: Our study focused on identifying and characterizing acid resistance determinants of B. suis and B. microti at different pH levels, revealing species-specific mechanisms in response to acid stress. The results showed that B. microti has rapid physiological adaptation to acid stress with specific differential gene expression, while B. suis response indicated increased protein misfolding under acid stress. The findings support the hypothesis that the enhanced acid stress resistance of B. microti is due to selective pressure for critical gene functionality and specific differential gene expression, leading to rapid adaptation.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Muhamad Mustafa, Jean-Yves Winum
Summary: Sulfur-containing functional groups play a significant role in medicinal chemistry and drug discovery. They have diverse applications and are found in a wide range of pharmacologically effective substances. The study reviews the recent research on organosulfur-based drug discovery and highlights the potential of sulfur-based compounds in lead compound development. Despite the growing importance of sulfur in medicinal chemistry, there is still a need for further exploration and development of synthetic methodologies for these functional groups.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Multidisciplinary
Jose Nunes da Silva Junior, Davila Zampieri, Antonio Jose Melo Leite Junior, Francisco Serra Oliveira Alexandre, Jean-Yves Winum, Andrea Basso, Andre Jalles Monteiro, Lucas Lima da Silva
Summary: A virtual Game-Based Tournament of Chemistry was developed as an alternative to traditional problem-solving classes, aimed at helping students review and understand organic acidity and basicity concepts. The tournament, based on a multilingual virtual board game, facilitated interactive and collaborative learning for students in an enjoyable activity. The findings showed that participating in the tournament resulted in better exam outcomes compared to traditional problem-solving classes.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Review
Microbiology
Alessandra Occhialini, Dirk Hofreuter, Christoph-Martin Ufermann, Sascha Al Dahouk, Stephan Kohler
Summary: The genus Brucella consists of twelve species of intracellular bacteria with varying zoonotic potential. While six of them are considered classical and known to cause brucellosis in terrestrial mammals, the remaining two species originate from marine mammals. Recent research has led to the discovery of four new species, as well as numerous strains isolated from a wide range of hosts, including cold-blooded animals. These newly identified species exhibit atypical phenotypes, such as higher growth rate, increased resistance to acid stress, motility, and lethality in murine infection models. This review provides an overview of the latest knowledge on these novel Brucella species, highlighting their phylogenetic positions, metabolic characteristics, acid stress resistance mechanisms, and behavior in well-established infection models. The comparison between classical and novel Brucella species and strains leads to a proposed more adapted terminology, distinguishing between core and non-core, and typical versus atypical brucellae.
Review
Chemistry, Multidisciplinary
Jose Nunes da Silva Junior, Jean-Yves Winum, Andrea Basso, Luca Gelati, Lisa Moni, Antonio Jose Melo Leite Junior, Jair Mafezoli, Davila Zampieri, Francisco Serra Oliveira Alexandre, Kimberly Benedetti Veja, Andre Jalles Monteiro
Summary: This paper presents a multi-lingual virtual card game that can be played on computers and smartphones. The game offers a fun and cooperative environment for students to play remotely or face-to-face with friends, while reviewing topics related to the structural theory of organic compounds. Evaluation from Brazilian and Italian undergraduate students showed positive feedback, and learning assessments indicate that the game promotes equivalent learning compared to traditional problem-solving classes.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Multidisciplinary
Beatrice Roy, Steghan Gasca, Jean-Yves Winum
Summary: This article presents the development of Chem'Sc@pe, an escape game activity designed for first-and second-year undergraduate students to review introductory organic chemistry concepts in a fun and collaborative environment. The game includes a game board, thematic cards with puzzles, tools such as molecular models, and an android-based application. Students work in teams to solve enigmas related to various organic chemistry topics in order to progress through the game. The activity was well-received by the students, who found it enjoyable, easy to play, and a beneficial learning experience.
JOURNAL OF CHEMICAL EDUCATION
(2023)
Article
Chemistry, Medicinal
Alessio Nocentini, Alessandro Bonardi, Carla Bazzicalupi, Vincenzo Alterio, Davide Esposito, Simona Maria Monti, Michael Smietana, Giuseppina De Simone, Claudiu T. Supuran, Paola Gratteri, Jean-Yves Winum
Summary: In this study, substituted 6-(1H-1,2,3-triazol-1-yl)benzoxaboroles were synthesized and characterized using in silico design. The 6-azidobenzoxaborole was introduced as a molecular platform for preparing libraries of inhibitors through a click chemistry strategy. Compound 20 showed high selectivity as hCAVII and IX inhibitors with inhibition constants below 30 nM. Crystallographic investigation validated the design hypothesis and provided explanations for the different inhibition behavior observed against five hCA isoforms. Overall, compound 20 was identified as a promising lead compound to develop novel anticancer agents targeting hCA IX and potent neuropathic pain relievers targeting hCA VII.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Zeyneb Ourdjini, Khairedine Kraim, Jean-Yves Winum, Eric Benoist, Achour Seridi
Summary: The aim of this study was to determine the reactivity and stability properties of a novel series of tricarbonylrhenium(I) complexes and analyze their binding affinity within the active site of carbonic anhydrases IX and XII. DFT and molecular docking methods were used for investigation. The results showed that bivalent ligands and their associated Re(I) complexes have higher reactivity and stability than monovalent ligands and their associated Re(I) complexes.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Pharmacology & Pharmacy
Amina Merabti, Sebastien Richeter, Claudiu T. Supuran, Sebastien Clement, Jean-Yves Winum
Summary: Photodynamic therapy (PDT) is an alternative cancer therapy strategy that depends on reactive oxygen species (ROS). However, hypoxia greatly reduces the therapeutic efficacy of PDT in solid tumors. Overexpressed tumor-associated carbonic anhydrases IX (hCA IX) and XII (hCA XII) are attractive drug targets for solid tumors. The current challenge lies in developing CA-targeted therapies that can overcome the limitation of hypoxia by combining photosensitizers and hCA IX/XII inhibitors.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Microbiology
Luca Freddi, Jorge A. de la Garza-garcia, Sascha Al Dahouk, Alessandra Occhialini, Stephan Koehler
Summary: This study reveals that atypical Brucella species can grow under anoxic conditions strictly dependent on nitrate, while classical species exhibit different behavior. Atypical Brucella species have a more efficient denitrification pathway and rapid consumption of nitrite, which may be related to their ability to colonize different hosts and rapid growth.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Alessio Nocentini, Andrea Angeli, Fabrizio Carta, Jean-Yves Winum, Raivis Zalubovskis, Simone Carradori, Clemente Capasso, William A. Donald, Claudiu T. Supuran
Summary: This review discusses the inhibition of carbonic anhydrase by inorganic anions, including various inhibitor classes and mechanisms. It also highlights the development of highly selective CAIs through rigorous X-ray crystallography experiments.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)