Article
Chemistry, Organic
Nirmala Mohanta, Pragnya Paramita Samal, Akanksha M. Pandey, Shankhajit Mondal, Sailaja Krishnamurty, Boopathy Gnanaprakasam
Summary: This study introduces a new synthetic methodology using In-(OTf)(3)-catalyzed α-vinylation of various hydroxy-functionalized quaternary carbon centers with in situ generated isobutylene from tert-butyl acetate. It demonstrates that tert-butyl acetate is a nonflammable feedstock and a readily available source for in situ production of vinyl substituents. Furthermore, Ni-(OTf)(2) shows excellent selectivity for methylallylation over vinylation as a catalyst. The sequential rearrangement of peroxyoxindole followed by nucleophilic attack by isobutylene leads to the formation of methylallyl-functionalized 1,4-benzoxazin-3-one derivatives. The reaction mechanism and selectivity are explained using kinetics and density functional theory studies.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Neurosciences
Josephine Labus, Kian-Fritz Roehrs, Jana Ackmann, Hristo Varbanov, Franziska E. Mueller, Shaobo Jia, Kathrin Jahreis, Anna-Lena Vollbrecht, Malte Butzlaff, Yvonne Schill, Daria Guseva, Katrin Boehm, Rahul Kaushik, Monika Bijata, Philippe Marin, Severine Chaumont-Dubel, Andre Zeug, Alexander Dityatev, Evgeni Ponimaskin
Summary: Tauopathies are a group of neurodegenerative diseases characterized by the buildup of hyperphosphorylated Tau protein. This study reveals the important role of 5-HT7R/CDK5 signaling in Tauopathy, suggesting that targeting 5-HT7R could be a promising therapeutic strategy for Tauopathies. Preventing Tau hyperphosphorylation and neurotoxicity by blocking constitutive 5-HT7R activity highlights a potential treatment approach for Tau-related disorders.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Chayma El Khamlichi, Flora Reverchon, Nadege Hervouet-Coste, Elodie Robin, Nicolas Chopin, Emmanuel Deau, Fahima Madouri, Cyril Guimpied, Cyril Colas, Arnaud Menuet, Asuka Inoue, Andrzej J. Bojarski, Gerald Guillaumet, Franck Suzenet, Eric Reiter, Severine Morisset-Lopez
Summary: This study demonstrates that Serodolin is a unique agonist/antagonist that modulates the biological functions of GPCRs through specific signaling pathways. Additionally, Serodolin has a significant analgesic effect on pain sensation and acts specifically through 5-HT7R. This research provides new insights into the molecular mechanism of 5-HT7R and the modulation of pain response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Rita Bardoni
Summary: The role of 5-HT7 receptors in modulating pain perception has been explored through in vivo studies using different pain models. While most studies have reported an antinociceptive effect of 5-HT7 receptor activation, some researchers have suggested a pronociceptive action. The discrepancies in the results could be explained by differences in pain models, animal species and gender, receptor types, agonists, and route of administration. This mini-review summarizes the main findings and discusses the expression patterns, cellular mechanisms, alterations in receptor function, and the future perspectives of 5-HT7 receptors in the pain system.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Neurosciences
Magdalena Kusek, Marcin Siwiec, Joanna Ewa Sowa, Bartosz Bobula, Wiktor Bilecki, Izabela Ciurej, Maria Kaczmarczyk, Tomasz Kowalczyk, Marzena Mackowiak, Grzegorz Hess, Krzysztof Tokarski
Summary: The research shows that activation of 5-HT7 receptors in the BA stimulates an activity-dependent enhancement of inhibitory input from local interneurons to BA principal neurons, providing insights into the possible involvement of BA serotonergic receptors in neuronal mechanisms underlying fear memory.
Article
Physiology
Bridget M. Seitz, Stephanie W. Watts, Gregory D. Fink
Summary: The 5-HT7 receptor plays a crucial role in both acute and chronic inflammation processes.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Neurosciences
Xiao-Cui Yuan, Xiang-Ji Yan, Li-Xia Tian, Yi-Xiao Guo, Yu-Long Zhao, Sani Sa'idu Baba, Yu-Ying Wang, Ling-Li Liang, Hong Jia, Lin-Ping Xu, Li Li, Han Lin, Fu-Quan Huo
Summary: The study demonstrated that the 5-HT7 receptor in the spinal cord activates GABAergic neurons through the Gs-cAMP-PKA pathway, and is involved in the EA-mediated inhibition of chronic pain in a mouse model of knee osteoarthritis (KOA).
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Romina Gonzalez-Pons, Kiera McRae, Janice M. Thompson, Stephanie W. Watts
Summary: The activation of 5-hydroxytryptamine can lower blood pressure by activating 5-HT7 receptors and inducing venodilation. Additionally, the 5-HT7 receptor restrains the activation of the 5-HT2A receptor, suggesting a potential role in reducing contraction.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Chemistry, Physical
Jolanta Jaskowska, Anna Karolina Drabczyk, Pawel Sliwa, Przemyslaw Jodlowski, Edyta Pindelska, Damian Kulaga, Przemyslaw Zareba, Zbigniew Majka, Agata Siwek, Malgorzata Wolak, Marcin Kolaczkowski
Summary: In our research, we used ultrasound to support a new synthesis method to find dual 5-HT1A/5-HT7 ligands from the long-chain arylpiperazine (LCAP) family. We tested the synthesis method on approved drugs with arylpiperazine structures and achieved satisfactory results. We then obtained compounds from the LCAPs group using the sonochemical method and selected two selective 5-HT1A/5-HT7 ligands.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Biochemistry & Molecular Biology
Jieon Lee, Diana Avramets, Byungsun Jeon, Hyunah Choo
Summary: Recent studies suggest that 5-HT7R could be a potential therapeutic target for the treatment of neurodevelopmental disorders by affecting neuronal morphology and modulating behavioral symptoms, offering a new approach to treating NDDs.
Article
Biochemistry & Molecular Biology
Marylene Bertrand, Frederic Szeremeta, Nadege Hervouet-Coste, Vincent Sarou-Kanian, Celine Landon, Severine Morisset-Lopez, Martine Decoville
Summary: This study used a Drosophila glioma model to investigate metabolic disturbances associated with glioma and identified the involvement of the 5-HT7R in glioma development. The study provides valuable insights into the metabolic pathways and potential treatment targets for glioma.
Article
Chemistry, Medicinal
Jakub Staron, Ryszard Bugno, Wojciech Pietrus, Grzegorz Satala, Stefan Mordalski, Dawid Warszycki, Agata Hogendorf, Adam S. Hogendorf, Justyna Kalinowska-Tluscik, Tomasz Lenda, Bogusiaw Pilarski, Andrzej J. Bojarski
Summary: Among all monoaminergic receptors, 5-HT6R stands out with the highest number of non-basic ligands, showing high affinity and selectivity. Despite a decade of research, the reason behind this phenomenon remains unclear. Through designed analogs, it was discovered that the binding to the receptor is mainly based on conformation, and additional functional groups can increase affinity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Flora Reverchon, Colleen Guillard, Lucile Mollet, Pascal Auzou, David Gosset, Fahima Madouri, Antoine Valery, Arnaud Menuet, Canan Ozsancak, Maud Pallix-Guyot, Severine Morisset-Lopez
Summary: This study reveals a dysregulation of 5-HT7 expression in natalizumab-treated multiple sclerosis (MS) patients, with an increase in 5-HT7 surface expression on T lymphocytes and CD4(+) T cell subsets. Activation of 5-HT7 receptor promotes the production of IL-10, suggesting its protective role in MS.
Article
Immunology
Hi-Joon Park, Sora Ahn, Hyangsook Lee, Dae-Hyun Hahm, Kyuseok Kim, Mijung Yeom
Summary: Acupuncture has been shown to effectively reduce itch symptoms in atopic dermatitis patients, potentially by blocking serotonin receptors to alleviate acute and chronic itch as well as skin inflammation.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Ho Young Kim, Ji Youn Lee, Chia-Ju Hsieh, Michelle Taylor, Robert R. Luedtke, Robert H. Mach
Summary: Previous studies have shown that endogenous dopamine competitively inhibits the binding of D-3 receptor antagonists. An SAR study on metoclopramide was conducted to develop an alternative scaffold for binding to the D-3 receptor. The study found that benzamide substituents and secondary binding fragments with aryl carboxamides resulted in excellent D-3 receptor affinities with subtype selectivity to the D-2 receptor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Applied
Timea Szabo, Andras Dancso, Balazs Volk, Matyas Milen
Summary: The study presents the first total synthesis of trigonostemine G, a newly isolated natural beta-carboline alkaloid, along with the synthesis of two structurally close derivatives. The key step in the syntheses involves a nucleophilic addition of 5-{[tert-butyl(dimethyl) silyl]oxy}-1H-indole to 1-formyl-beta-carboline building blocks.
NATURAL PRODUCT RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Michael Spedding, Sumantra Chattarji, Charlotte Spedding, Therese M. Jay
Summary: This review focuses on key brain circuits and their role in health and disease, as well as the impact of upbringing, stress, genetics, and pharmacotherapy on psychiatric diseases.
Review
Cell Biology
Alexandra Bouscary, Cyril Quessada, Frederique Rene, Michael Spedding, Bradley J. Turner, Alexandre Henriques, Shyuan T. Ngo, Jean-Philippe Loeffler
Summary: Sphingolipids play crucial roles in the development and maintenance of the nervous system, with dysregulated metabolism being linked to specific neurodegenerative diseases. Current research primarily focuses on ALS, seeking potential treatments that target sphingolipid metabolism in neurodegenerative diseases.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Simon D. Harding, Jane F. Armstrong, Elena Faccenda, Christopher Southan, Stephen P. H. Alexander, Anthony P. Davenport, Adam J. Pawson, Michael Spedding, Jamie A. Davies
Summary: The IUPHAR/BPS Guide to PHARMACOLOGY has expanded its content in the past two years, focusing on infection, malaria, and antibiotic resistance. It has included a new family of Coronavirus proteins and collaborated with Medicines for Malaria Venture and AntibioticDB to enhance coverage of malaria pharmacology and antibacterials.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Organic
Gyorgyi Kovanyi-Lax, Csilla Hargitai, Peter Abranyi-Balogh, Tamas Nagy, Gabor Toth, Zsofia Garadi, Gabor Nemeth, Angela Pandur, Simon Horvath, Andras Dancso, Gyula Simig, Balazs Volk
Summary: In this study, the reactions of ortho-(pivaloylaminomethyl)benzaldehydes using boron trifluoride diethyl etherate (BF3 center dot OEt2) as the catalyst were described, and the formation of a new dimer-like keto compound and an oxoindene-type by-product was observed. Detailed characterization and theoretical calculations support the proposed mechanisms and explain the product distribution.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Physical
Gabor Gyorke, Andras Dancso, Balazs Volk, Laszlo Bezur, David Hunyadi, Imre Szaloki, Matyas Milen
Summary: Copper-containing minerals play a vital role in the economy and the origin of life. This study presents a copper mineral-catalyzed method for synthesizing arylated amide derivatives, utilizing the catalytic effect of readily available minerals.
Article
Pharmacology & Pharmacy
Bence Sipos, Ildiko Csoka, Nimrod Szivacski, Maria Budai-Szucs, Zsuzsanna Schelcz, Istvan Zupko, Piroska Szabo-Revesz, Balazs Volk, Gabor Katona
Summary: Intranasally administered NSAIDs can be effective in pain management, and nanoemulsions can enhance drug absorption and bioavailability, providing an advanced drug delivery system.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Applied
Balint Petho, Gabor B. Szilagyi, Bela Mengyel, Tamas Nagy, Ferenc Farkas, Katalin Katai-Fadgyas, Balazs Volk
Summary: A flow chemical approach was developed to mitigate the hazards associated with aromatic nitration and catalytic hydrogenation. A four-step uninterrupted process, based on a newly developed heterogeneous flow reactor system and a custom-made liquid-liquid extractor, was successfully used for the efficient production of a key intermediate of the drug candidate afizagabar (S44819).
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Organic
Balint Nyulasi, Tamara Teski, Andras Gy. Nemeth, Sara Sprober, Gyula Simig, Balazs Volk
Summary: The significant pharmacological activity of 2,3-benzodiazepine-4-ones has increased interest in this compound family. However, there is limited literature on the closely related 2,3,4-benzothiadiazepine 2,2-dioxides. In this study, a new synthetic route was explored using highly versatile intermediates to expand the reaction to a wider range of aromatic substitutions and to prepare 5-alkyl and 5-H derivatives.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Attila M. Remete, Melinda Nonn, Balazs Volk, Lorand Kiss
Summary: Due to the relevance of fluorine-containing organic molecules in drug research, the synthesis of organofluorine scaffolds is highly significant in synthetic organic chemistry. Trifluoromethylative difunctionalizations of carbon-carbon multiple bonds, with the introduction of a CF3 group and another function, have great potential. Alkynyltrifluoromethylation reactions, especially, are gaining interest in synthetic chemistry. This review summarizes recent developments in alkynyltrifluoromethylation reactions, including reactions involving intramolecular alkynyl migration and intermolecular transformation, as well as reactions of alkynes.
SYNTHESIS-STUTTGART
(2022)
Article
Cell Biology
Michael Spedding, Claude Sebban, Therese M. Jay, Cyril Rocher, Brigitte Tesolin-Decros, Paul Chazot, Esther Schenker, Gabor Szenasi, Gyorgy Levay, Katalin Megyeri, Jozsef Barkoczy, Laszlo G. Harsing, Ian Thomson, Mark O. Cunningham, Miles A. Whittington, Lori-An Etherington, Jeremy J. Lambert, Ferenc A. Antoni, Istvan Gacsalyi
Summary: Dysfunction in the H-PFC circuit is a critical factor in schizophrenia, and a new drug called EGIS 11150 has been found to induce theta rhythm, enhance H-PFC coherence, and restore long-term potentiation in this circuit. This suggests that phenotypical screening on H-PFC connectivity can uncover novel antipsychotics.
Article
Chemistry, Organic
Matyas Milen, Balint Nyulasi, Tamas Nagy, Gyula Simig, Balazs Volk
Summary: A novel synthesis approach for the late-stage tetracyclic key intermediate of lumateperone starting from commercially available quinoxaline is described. The tetracyclic skeleton was constructed efficiently using Fischer indole synthesis, with the advantage of inexpensive starting material and avoidance of borane-based reduction step, providing potential for scalability.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Christopher N. Connolly, Stephen P. H. Alexander, Jamie A. Davies, Michael Spedding
Summary: The article proposes the application of standard pharmacological principles to assess the dosing of the environment and suggests the concept of an "environmental therapeutic window" for risk assessment of pesticides. To achieve this, a freely accessible database containing quantitative data on pesticide action is needed.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Meeting Abstract
Toxicology
M. Spedding
TOXICOLOGY LETTERS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
M. Fazzari, A. Henriques, G. Lunghi, L. Mauri, M. G. Ciampa, G. Tedeschi, N. Mitro, S. Sonnino, M. Spedding, E. Chiricozzi
