Article
Biochemistry & Molecular Biology
Carlotta Bon, Ting-Rong Chern, Elena Cichero, Terrence E. O'Brien, Stefano Gustincich, Raul R. Gainetdinov, Stefano Espinoza
Summary: Trace amine-associated receptor 5 (TAAR5) is expressed in the olfactory epithelium and limbic brain regions, and is involved in the regulation of emotional behavior and adult neurogenesis. Two identified mTAAR5 antagonists inhibit TMA-induced cAMP production and downstream signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yunjie Wang, Zhaofeng Liu, Jing Lu, Wenyan Wang, Lin Wang, Yifei Yang, Hongbo Wang, Liang Ye, Jianzhao Zhang, Jingwei Tian
Summary: This study discovered two TAAR1 agonists, among which compound 50B demonstrated superior inhibition of MK801-induced schizophrenia-like behavior and favorable druggability, as well as the ability to penetrate the blood-brain barrier.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Alex Maolanon, Athanasios Papangelis, David Kawiecki, Tung-Chung Mou, Jed T. Syrenne, Feng Yi, Kasper B. Hansen, Rasmus P. Clausen
Summary: A versatile stereoselective route was developed for synthesizing new 2'-(S)-CCG-IV analogues, allowing for late stage diversification. The evaluation of these analogues demonstrated the potential for developing subtype-specific NMDA receptor agonists with varying potency and efficacy. The crystal structure analysis of the agonist binding domain provided insights into the structural determinants of agonist efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ru Wang, Ting-Ting Du, Wen-Qiang Liu, Yi-Chen Liu, Ya-Dong Yang, Jin-Ping Hu, Ming Ji, Bei-Bei Yang, Li Li, Xiao-Guang Chen
Summary: By designing and testing the inhibitory effects of compounds on the STAT3 pathway, researchers have successfully developed a novel selective STAT3 inhibitor that can inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. This compound has demonstrated anti-proliferative and apoptotic effects on STAT3-overactivated cancer cells and exhibited promising anti-tumor efficacy in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yongtao Li, Wenwei Lin, Sergio C. Chai, Jing Wu, Kavya Annu, Taosheng Chen
Summary: In this study, a selective and potent PXR antagonist was discovered through structural optimization of a series of compounds. This finding provides novel PXR inhibitors for basic research and future clinical studies and sheds light on reducing compound's binding affinity to PXR.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Martina Salerno, Carmine Varricchio, Federica Bevilacqua, Dirk Jochmans, Johan Neyts, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Different viruses, such as enterovirus 71, rely on the host enzyme METTL3 to complete their cytoplasmic life cycle stages. By modulating the activity of this enzyme, it is possible to interfere with a broad range of viral infections. In this study, a series of nucleoside analogues were designed as inhibitors of human METTL3 to target multiple viral infections. Through molecular docking studies and synthesis, several novel and potent inhibitors of enterovirus 71 were identified.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shizhen Zhao, Le Wang, Jie Wang, Chenwei Wang, Shaowei Zheng, Yajie Fu, Yunfu Li, Wei-Dong Chen, Ruifang Hou, Dongbin Yang, Yan-Dong Wang
Summary: TGR5 is an important target for the treatment of non-alcoholic steatohepatitis, type 2 diabetes mellitus, and obesity. Novel compounds have been discovered with excellent agonist activity.
Article
Chemistry, Medicinal
Douglas L. Orsi, Elisabeth Pook, Nico Braeuer, Anders Friberg, Philip Lienau, Christopher T. Lemke, Timo Stellfeld, Ulf Bruggemeier, Vera Putter, Hanna Meyer, Maria Baco, Stephanie Tang, Andrew D. Cherniack, Lindsay Westlake, Samantha A. Bender, Mustafa Kocak, Craig A. Strathdee, Matthew Meyerson, Knut Eis, Jonathan T. Goldstein
Summary: In muscle-invasive luminal bladder cancer, activating PPARG can be a potential therapeutic approach. This study identified a series of covalent inverse-agonists of PPAR gamma that can regulate PPAR gamma target genes and exhibit antiproliferative effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Behavioral Sciences
Seetal Dodd, Andre F. Carvalho, Basant K. Puri, Michael Maes, Chiara C. Bortolasci, Gerwyn Morris, Michael Berk
Summary: TAARs are a group of receptors with multiple subfamilies that play important roles in homeostasis, olfaction, and monoamine systems. They are potential therapeutic targets for various mental disorders and cancers. Modulators of TAAR1 show efficacy in animal models, but further research is needed to establish their applicability.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Lingna Guo, Wenxuan Dai, Zhengrong Xu, Qiaoyi Liang, Eliot T. Miller, Shengju Li, Xia Gao, Maude W. Baldwin, Renjie Chai, Qian Li
Summary: The family of trace amine-associated receptors (TAARs) is distantly related to G protein-coupled biogenic aminergic receptors. They are found in the brain and olfactory epithelium, and their functional relationships in different subfamilies and species are still uncertain. Through phylogenetic analysis, this study reveals the evolutionary patterns and ligand recognition profiles of TAARs and shows functional convergence and segregation in different species.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Chemistry, Medicinal
Douglas L. Orsi, Elisabeth Pook, Nico Braeuer, Anders Friberg, Philip Lienau, Christopher T. Lemke, Timo Stellfeld, Ulf Bruggemeier, Vera Putter, Hanna Meyer, Maria Baco, Stephanie Tang, Andrew D. Cherniack, Lindsay Westlake, Samantha A. Bender, Mustafa Kocak, Craig A. Strathdee, Matthew Meyerson, Knut Eis, Jonathan T. Goldstein
Summary: This study reveals a series of covalent inverse-agonists of PPAR gamma that interact with corepressors NCOR1 and NCOR2, resulting in regulation of PPAR gamma target genes and antiproliferative effects in sensitive cell lines. Despite their imperfect physicochemical properties, these compounds show modest pharmacodynamic target regulation in vivo, making them novel tools for probing the biology of PPAR gamma inverse-agonism in vitro.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ilya S. Zhukov, Larisa G. Kubarskaya, Inessa Karpova, Anastasia N. Vaganova, Marina N. Karpenko, Raul R. Gainetdinov
Summary: Trace amine-associated receptor 5 (TAAR5) plays a crucial role in perceiving odors, regulating emotions, and potentially treating neuropsychiatric disorders. Research suggests that TAAR5 deficiency may lead to minor negative effects on hematological parameters, while having minimal impact on other blood-related factors. Further study is needed to fully understand the implications of TAAR5 gene knockout in erythropoiesis and eryptosis processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mingcheng Qian, Zhijie Luo, Wenwen Hou, Jingjing Sun, Xin Lu, Qianxi Zhang, Yi Wu, Caile Xue, Shuai Zhao, Xin Chen
Summary: In this study, fourteen new cholic acid derivatives were designed and synthesized, and one of them, B1, was found to be a highly potent TGR5 agonist, which can be used as a lead compound for further study.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ilya S. S. Zhukov, Anastasia N. N. Vaganova, Ramilya Z. Z. Murtazina, Lyubov S. S. Alferova, Elena I. I. Ermolenko, Raul R. R. Gainetdinov
Summary: Trace amine-associated receptors (TAAR1-TAAR9) play an important role in the central nervous system and TAAR9 deletion leads to alterations in the periphery. TAAR9 is identified in intestinal tissues and is co-expressed with genes involved in intestinal mucosa homeostasis and function. Furthermore, TAAR9 may play a role in regulating peripheral dopaminergic transmission. Fecal microbiome analysis shows significant differences in the microbial composition between TAAR9-KO and wild-type rats, with certain bacterial families almost completely absent in TAAR9-KO rats.
Article
Biochemistry & Molecular Biology
Huoming Huang, Xinwei Li, Wei Guo, Chen Zhu, Yuanyuan Qian, Qing Shen, Xuejun Xu, Wei Li, Yujun Wang, Wei Fu
Summary: Pain is associated with many diseases, and opioid analgesics are effective but have limitations due to side effects. A study focused on designing and synthesizing novel analogues based on an active metabolite of tramadol, leading to the discovery of compound 23 as a potent and highly selective MOR agonist. Structure-activity relationship exploration revealed that the linker and substituent pattern play a crucial role in binding affinity and selectivity.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Applied
Jasmine Esposito Salsano, Diana Pinto, Francisca Rodrigues, Alessandro Saba, Clementina Manera, Maria Digiacomo, Marco Macchia
Summary: The study focused on developing a method to isolate and purify oleocanthalic acid from olive oil, and then used the pure oleocanthalic acid to develop a high performance liquid chromatography method for qualitative and quantitative analysis of oleocanthalic acid content in olive oil. Preliminary assessment showed that oleocanthalic acid has a higher quenching efficiency for HOCl than O-2(center dot-).
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
(2022)
Article
Pharmacology & Pharmacy
Francesca Gado, Costanza Ceni, Rebecca Ferrisi, Giulia Sbrana, Lesley A. Stevenson, Marco Macchia, Roger G. Pertwee, Simone Bertini, Clementina Manera, Gabriella Ortore
Summary: In this study, we developed novel compounds with peripheral CB1R selective antagonistic activity and discovered that two compounds, C7 and C10, showed possible allosteric behavior. Computational studies revealed that these compounds preferentially interacted with the experimental binding site for negative allosteric modulators.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Francesca Gado, Rebecca Ferrisi, Sarah Di Somma, Fabiana Napolitano, Kawthar A. Mohamed, Lesley A. Stevenson, Simona Rapposelli, Giuseppe Saccomanni, Giuseppe Portella, Roger G. Pertwee, Robert B. Laprairie, Anna Maria Malfitano, Clementina Manera
Summary: This study synthesized and characterized new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. These compounds showed anticancer activity by modulating the cAMP response and modulating ERK1/2 expression through a CB2R-mediated mechanism.
Article
Food Science & Technology
Jasmine Esposito Salsano, Maria Digiacomo, Doretta Cuffaro, Simone Bertini, Marco Macchia
Summary: The health benefits of extra-virgin olive oil are closely related to the presence of phenolic compounds. This study reveals that storage conditions are crucial in controlling the concentration of phenolic compounds in olive oil, with light exposure and higher temperatures leading to more significant degradation.
Article
Chemistry, Medicinal
Andrea Bacci, Francesca Corsi, Massimiliano Runfola, Simona Sestito, Ilaria Piano, Clementina Manera, Giuseppe Saccomanni, Claudia Gargini, Simona Rapposelli
Summary: Overproduction of reactive oxygen species (ROS) and metal imbalance are common features in neurodegenerative diseases (NDDs). In this study, a series of 8-quinoline-N-substituted derivatives with natural antioxidant properties were designed to target ROS in NDDs. The compounds showed the ability to chelate copper, a metal involved in ROS-induced degeneration, and scavenge oxygen radicals. In addition, selected compounds 4 and 5 demonstrated cytoprotective effects in an in vitro model of oxidative stress. These findings provide a starting point for the potential application of these compounds in retinal neurodegenerative diseases.
Article
Chemistry, Medicinal
Elena Cichero, Federica Rapetti, Matteo Lusardi, Naomi Scarano, Silvana Alfei, Paola Altieri, Silvano Garibaldi, Pietro Ameri, Maria Grazia Signorello, Chiara Brullo
Summary: In the past few years, we have developed a large library of new selective phosphodiesterase 4D (PDE4D) inhibitors. These inhibitors retain the catechol portion of the well-known PDE4 inhibitor Rolipram, with different substitutions in place of the lactam group. Through molecular docking studies, we designed and synthesized new compounds that showed potential PDE4 inhibitory activity, especially with the enzyme's flat aromatic residues. In vitro assays confirmed their antioxidant/anti-inflammatory activity, similar to other known PDE4 inhibitors.
Article
Biochemistry & Molecular Biology
Naomi Scarano, Elena Abbotto, Francesca Musumeci, Annalisa Salis, Chiara Brullo, Paola Fossa, Silvia Schenone, Santina Bruzzone, Elena Cichero
Summary: This article focuses on the selective inhibitors of SIRT2 enzyme. By using SBVS method, a potential molecular scaffold for designing new SIRT2 inhibitors was identified. Experimental results showed that this molecular scaffold exhibited strong SIRT2 inhibitory activity, validating the effectiveness of the research strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Alena A. Kozlova, Elena Rubets, Magdalini R. Vareltzoglou, Natalia Jarzebska, Vinitha N. Ragavan, Yingjie Chen, Jens Martens-Lobenhoffer, Stefanie M. Bode-Boeger, Raul R. Gainetdinov, Roman N. Rodionov, Nadine Bernhardt
Summary: In this study, the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance was investigated. The results showed that DDAH1-ko mice exhibited changes in exploratory behavior, amphetamine response, and dopamine metabolite levels. Female mice showed the most significant amphetamine response, supporting the potential implication of the DDAH/ADMA pathway in central nervous system processes.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Nutrition & Dietetics
Doretta Cuffaro, Simone Bertini, Marco Macchia, Maria Digiacomo
Summary: This study examines the combination of olive leaf extract and extra virgin olive oil extract, which shows improved antioxidant and anti-inflammatory properties compared to the singular olive oil extract. This extract may have potential in the field of nutraceuticals.
Article
Oncology
Andrea Caddeo, Marina Serra, Francesca Sedda, Andrea Bacci, Clementina Manera, Simona Rapposelli, Amedeo Columbano, Andrea Perra, Marta Anna Kowalik
Summary: The study found that TG68 has a therapeutic effect on NAFLD-associated hepatocarcinogenesis. It can significantly reduce hepatic fat accumulation, improve lipid and glucose levels, and restore the differentiation status of hepatocytes. This novel therapeutic strategy shows promise in the treatment of NAFLD-associated hepatocarcinogenesis.
FRONTIERS IN ONCOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Graeme Barker, Simona Rapposelli
Article
Biochemistry & Molecular Biology
Doretta Cuffaro, Diana Pinto, Ana Margarida Silva, Andrea Bertolini, Simone Bertini, Alessandro Saba, Marco Macchia, Francisca Rodrigues, Maria Digiacomo
Summary: This study investigates the antioxidant effects of high-value polyphenol oleocanthal (OC) and its main metabolites, tyrosol (Tyr) and oleocanthalic acid (OA), as well as their impact on cell viability. The results demonstrate the promising properties of OC, OA, and Tyr against oxidative diseases, including their ability to scavenge reactive oxygen species and permeate the intestinal membrane.
Article
Biochemistry & Molecular Biology
Rebecca Ferrisi, Beatrice Polini, Caterina Ricardi, Francesca Gado, Kawthar A. A. Mohamed, Giovanna Baron, Salvatore Faiella, Giulio Poli, Simona Rapposelli, Giuseppe Saccomanni, Giancarlo Aldini, Grazia Chiellini, Robert B. B. Laprairie, Clementina Manera, Gabriella Ortore
Summary: We have developed a new generation of ligands (JR compounds) that target the CB2R. These compounds combine the pharmacophoric portion of CB2R positive allosteric modulator (EC21a) with that of CB2R selective orthosteric agonist (LV62). Among the tested compounds, JR22a showed dualsteric behavior as a CB2R ligand. Computational studies confirmed the binding mode of JR22a at CB2R, and its potential to prevent neuroinflammation was investigated using a human microglial cell model.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Andrea Marco Caddeo, Marta Anna Kowalik, Marina Serra, Simona Rapposelli, Amedeo Columbano, Andrea Perra
JOURNAL OF HEPATOLOGY
(2022)