Review
Physiology
Akiyuki Taruno, Michael D. Gordon
Summary: Salt taste is one of the most complex and puzzling basic tastes, and animals use it to ingest the right amount of salt. The concentration-valence relationship of salt taste is universally observed in terrestrial animals, and there are multiple taste pathways involved. Although the molecular and cellular mechanisms underlying salt taste have been partially uncovered, there is still much unknown.
ANNUAL REVIEW OF PHYSIOLOGY
(2023)
Article
Oncology
Darya Fayzullina, Semyon Yakushov, Kamilla Kantserova, Elizaveta Belyaeva, Denis Aniskin, Sergey Tsibulnikov, Nafisa Fayzullina, Stanislav Kalinin, Olga Romantsova, Peter S. Timashev, Brett A. Schroeder, Ilya V. Ulasov
Summary: This study discovered that carbonic anhydrase II (CAII) inhibitors can inhibit the growth and invasion of Ewing sarcoma (ES) cells through multiple mechanisms, trigger cell death, and have potential therapeutic effects. The results suggest that cytosolic CAII may be a promising target for ES treatment, and CAII inhibitors can be considered as potential single-agent or combination antitumor agents in the treatment of ES.
Article
Chemistry, Multidisciplinary
Giulia Degiacomi, Beatrice Gianibbi, Deborah Recchia, Giovanni Stelitano, Giuseppina Ivana Truglio, Paola Marra, Alessandro Stamilla, Vadim Makarov, Laurent Robert Chiarelli, Fabrizio Manetti, Maria Rosalia Pasca
Summary: To combat drug-resistant strains of Mycobacterium tuberculosis, new targets are needed to develop effective drugs. This study demonstrates a workflow for validating new targets and inhibitors using genetic, in silico, and enzymological approaches. The essential role of CanB in the survival of the pathogen was confirmed through conditional mutants, and three molecules were selected as inhibitors of CanB, showing bactericidal activity against wild-type and conditional mutants of M. tuberculosis.
Article
Physiology
Kathleen Boyne, Deborah A. Corey, Pan Zhao, Binyu Lu, Walter F. Boron, Fraser J. Moss, Thomas J. Kelley
Summary: Several aspects of CF epithelial cells are altered, including impaired lipid regulation, disrupted intracellular transport, and impaired microtubule regulation. This study demonstrates that the loss of CFTR function leads to a decrease in CA2 expression and activity, which may contribute to the observed cell signaling alterations in CF.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Chemistry, Medicinal
Gustavo Provensi, Alessia Costa, Barbara Rani, Maria Vittoria Becagli, Fabio Vaiano, Maria Beatrice Passani, Damiano Tanini, Antonella Capperucci, Simone Carradori, Jacobus P. Petzer, Anel Petzer, Daniela Vullo, Gabriele Costantino, Patrizio Blandina, Andrea Angeli, Claudiu T. Supuran
Summary: This study reported the synthesis of β-arylchalcogeno amines with structural similarity to amphetamine, which showed good activation properties for certain enzymes in the brain. In vivo evaluation demonstrated the procognitive effects of these compounds without causing unwanted side effects. These findings suggest the potential utility of these compounds for improving cognitive decline associated with neurodegenerative and psychiatric diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ozlem Akgul, Srishti Singh, Jacob T. Andring, Robert McKenna, Silvia Selleri, Fabrizio Carta, Andrea Angeli, Claudiu T. Supuran
Summary: A series of taurine substituted sulfonamide derivatives with ureido moiety at the tail section were synthesized as selective inhibitors of tumor associated human Carbonic Anhydrase (CA) IX and XII. These derivatives showed a strong dependence on the presence of ureido moiety and demonstrated highly stabilized ligand-protein complex with specific amino acid residues in both hCA II and hCA IX-mimic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Shubham Kumar, Sandeep Rulhania, Shalini Jaswal, Vikramdeep Monga
Summary: Carbonic anhydrase is an important enzyme involved in various physiological and pathological processes, with 16 different isoforms in humans. Inhibitors targeting different isoforms of carbonic anhydrase have clinical applications in treating various diseases, but current drugs lack selectivity leading to undesired side effects. Efforts are being made to develop novel isoform-selective inhibitors of carbonic anhydrase for therapeutic implications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xiaojing Huang, Daniel Winter, Dominic. J. J. Glover, Claudiu. T. T. Supuran, William. A. A. Donald
Summary: Carbonic anhydrases (CAs) are metalloenzymes that play important roles in cellular processes and have been implicated in various diseases. Phosphorylation, a common post-translational modification of CAs, can significantly impact their catalytic activity and drug-binding capabilities. This study highlights the potential regulatory role of phosphorylation in CA activity and its effect on small molecule drug binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Marta Meneghello, Ana Rita Oliveira, Aurore Jacq-Bailly, Ines A. C. Pereira, Christophe Leger, Vincent Fourmond
Summary: Mo/W formate dehydrogenases catalyze the reversible reduction of CO2 to formate, and it has been definitively demonstrated through an electrochemical method that the substrate is indeed CO2, not a hydrated species like HCO3-.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Medicine, General & Internal
Mohammed Al-Zubaidi, Pravin Viswambaram, Steve McCombie, Elizabeth Liow, Nat Lenzo, Tom Ferguson, Andrew D. Redfern, Richard Gauci, Dickon Hayne
Summary: Bladder cancer is a lethal disease with limited conventional imaging modalities for accurate staging. This study aims to investigate the use of (89)Zirconium-labelled girentuximab PET in the staging of bladder and urothelial carcinomas.
Article
Biochemistry & Molecular Biology
Amarjyoti Das Mahapatra, Aarfa Queen, Mohd Yousuf, Parvez Khan, Afzal Hussain, Md. Tabish Rehman, Mohamed F. Alajmi, Bhaskar Datta, Md. Imtaiyaz Hassan
Summary: Inhibitors of carbonic anhydrase have the potential to address various diseases. This research focuses on developing a new scaffold, oxazole-5(4H)-one derivatives, for the selective inhibition of human carbonic anhydrase VA (hCAVA). Two compounds show high binding affinity and inhibit the expression of CAVA and GLUT4 in adipocytes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Chemistry, Multidisciplinary
Cristhian Molina-Fernandez, Patricia Luis
Summary: The use of immobilized carbonic anhydrase as a novel approach for CO2 capture presents a promising alternative to address cost and environmental issues. Current research focuses on developing different carriers and immobilization strategies to achieve stability and activity compared to free enzyme in solution.
JOURNAL OF CO2 UTILIZATION
(2021)
Article
Medicine, Research & Experimental
Jiajie Qian, Qianyun Shen, Tianfang Zhang, Jing Chen, Lifeng Chen, Yang Dong, Ren Yan, Zuobing Chen
Summary: CAR14 plays an important role in protecting the liver against bile acid toxicity. The study found that Car14 gene knockout results in liver dysfunction, hepatic fibrosis, bile duct lesions, increased hepatic bile acid levels, and altered bile acid compositions in BDL mice. Car14 knockout also suppresses the uptake and synthesis of bile acids in the liver.
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Clemente Capasso, Alessio Nocentini, Claudiu T. Supuran
Summary: A series of new sulfocoumarins with different substitutions were synthesized and screened as prodrug inhibitors of cancer-associated carbonic anhydrases. Sulfocoumarin 15 was found to be the most potent and selective inhibitor.
Article
Biochemistry & Molecular Biology
Vaha Akbary Moghaddam, Vesal Kasmaeifar, Zainab Mahmoodi, Hossein Ghafouri, Omid Saberi, Asadollah Mohammadi
Summary: A novel derivative of sulfamethoxazole named ZM-093 was synthesized and characterized through experimental and computational analysis, showing significant inhibitory effect against the cancer-related protein HSP70, potentially through binding to its substrate-binding domain. Additionally, a new method for evaluating the inhibitory activity of ligands to HSP70 based on protonography was introduced.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Thibaut Boibessot, David Benimelis, Patrick Meffre, Zohra Benfodda
Article
Environmental Sciences
Lara Sassine, Corinne Le Gal La Salle, Mahmoud Khaska, Patrick Verdoux, Patrick Meffre, Zohra Benfodda, Benoit Roig
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2017)
Article
Chemistry, Medicinal
Thibaut Boibessot, Christopher P. Zschiedrich, Alexandre Lebeau, David Benimelis, Catherine Dunyach-Remy, Jean-Philippe Lavigne, Hendrik Szurmant, Zohra Benfodda, Patrick Meffre
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Alexandre Lebeau, Cyril Abrioux, David Benimelis, Zohra Benfodda, Patrick Meffre
MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Organic
Thibaut Boibessot, David Benimelis, Marion Jean, Zohra Benfodda, Patrick Meffre
Article
Environmental Sciences
Valentin Duvauchelle, Elsa Causse, Julien Michon, Patrick Rateau, Karine Weiss, Patrick Meffre, Zohra Benfodda
Summary: The survey in France revealed moderate antibiotic usage but continued misconceptions about appropriate practices and knowledge regarding antibiotics. Students majoring in biology showed a higher awareness of antibiotic resistance risk and health consequences compared to those majoring in mathematics. It was emphasized that young students, regardless of their field of expertise, should be provided with a minimum level of knowledge on the topic.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Biochemistry & Molecular Biology
Valentin Duvauchelle, David Benimelis, Patrick Meffre, Zohra Benfodda
Summary: A new approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using alpha-trifluoromethyl ketones is described. The study demonstrates the site-selective electrophilic aromatic substitution on the C-3 atom of an unprotected 5-phenylthiophen-2-amine moiety. The reaction proceeds smoothly without the use of metal or catalyst, resulting in good to excellent yields.
Article
Chemistry, Medicinal
Valentin Duvauchelle, Patrick Meffre, Zohra Benfodda
Summary: 2-Aminothiophene is an attractive core structure that exhibits broad biological activities and serves as a precursor for the synthesis of active thiophene-containing compounds. Compounds derived from 2-aminothiophene are promising in medicinal chemistry as selective inhibitors and modulators, showing effective pharmacological properties in clinical studies of specific diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Cyril Bourouh, Emilie Courty, Laure Rolland, Gianni Pasquetti, Xavier Gromada, Nabil Rabhi, Charlene Carney, Maeva Moreno, Raphael Boutry, Emilie Caron, Zohra Benfodda, Patrick Meffre, Julie Kerr-Conte, Francois Pattou, Philippe Froguel, Amelie Bonnefond, Frederik Oger, Jean-Sebastien Annicotte
Summary: The study reveals the critical role of E2f1 in regulating beta cell function and suggests molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways.
Article
Biochemistry & Molecular Biology
Alexandre Gonzalez, Zohra Benfodda, David Benimelis, Jean-Xavier Fontaine, Roland Molinie, Patrick Meffre
Summary: This study investigated the chemical diversity of volatile organic compounds (VOCs) released by 14 Tillandsia species using headspace solid phase microextraction coupled with gas chromatography-mass spectrometry. A total of 65 VOCs were identified, with 6 to 25 compounds found in each species. Ten species and hybrids shared a similar aromatic profile with 8 predominant compounds, while two faint-scented species exhibited a unique profile rich in monoterpenes or phenylpropanoids/benzenoids.
Review
Chemistry, Multidisciplinary
Valentin Duvauchelle, Patrick Meffre, Zohra Benfodda
Summary: Due to pollution and the rising energy demand, the design of new synthetic reactions that meet the principles of green chemistry has become increasingly important. This review focuses on new synthetic routes to 2-aminothiophenes, including multicomponent reactions, homogeneously- or heterogeneously-catalyzed reactions, with an emphasis on green pathways.
ENVIRONMENTAL CHEMISTRY LETTERS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Christopher Zschiedrich, Thibaut Boibessot, Alexandre Lebeau, David Benimelis, Zohra Benfodda, Patrick Meffre, Hendrik Szurmant
Meeting Abstract
Biochemistry & Molecular Biology
Thibaut Boibessot, Zohra Benfodda, Alexandre Lebeau, David Benimelis, Patrick Meffre
Meeting Abstract
Biochemistry & Molecular Biology
Zohra Benfodda, David Benimelis, Valerie Rolland, Patrick Meffre
Meeting Abstract
Biochemistry & Molecular Biology
Stephanie Ortial, Rajesh Dave, Zohra Benfodda, David Benimelis, Patrick Meffre
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)
