Article
Chemistry, Medicinal
Jin-Ling Huo, Shuai Wang, Xiao-Han Yuan, Bin Yu, Wen Zhao, Hong-Min Liu
Summary: Compound 6i showed potent anti-proliferative activity against MGC-803 with good safety in vivo. Mechanistic studies revealed that 6i induced apoptosis in MGC-803 cells through multiple pathways, suggesting its potential as a template for anti-cancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Stephanie Federico, Margherita Persico, Letizia Trevisan, Chiara Biasinutto, Giovanni Bolcato, Veronica Salmaso, Tatiana Da Ros, Teresa Gianferrara, Filippo Prencipe, Sonja Kachler, Karl-Norbert Klotz, Sabrina Pacor, Stefano Moro, Giampiero Spalluto
Summary: This study identified a new selective antagonist for the A(3) adenosine receptor, which showed pro-proliferative effects on cancer cells. These findings provide a foundation for further investigation of its mechanism and potential therapeutic applications.
Article
Chemistry, Medicinal
Maria Chiara Pismataro, Tommaso Felicetti, Chiara Bertagnin, Maria Giulia Nizi, Anna Bonomini, Maria Letizia Barreca, Violetta Cecchetti, Dirk Jochmans, Steven De Jonghe, Johan Neyts, Arianna Loregian, Oriana Tabarrini, Serena Massari
Summary: The study identified 1,2,4-triazolo[1,5-a] pyrimidine (TZP) as a suitable scaffold for developing anti-influenza virus compounds, with compound 22 showing high activity. Furthermore, the research highlighted the potential of TPZ scaffold in the search for anti-coronavirus agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Fabian Wesseler, Stefan Lohmann, Daniel Riege, Jonas Halver, Aileen Roth, Christian Pichlo, Sabrina Weber, Masanari Takamiya, Eva Mueller, Jana Ketzel, Jana Flegel, Adrian Gihring, Sepand Rastegar, Jessica Bertrand, Ulrich Baumann, Uwe Knippschild, Christian Peifer, Sonja Sievers, Herbert Waldmann, Dennis Schade
Summary: Phenotypic drug discovery is an important research approach, and its success relies on the quality of the underlying model system. In this study, a stem cell-based method was used to discover a new activator for the bone morphogenetic protein pathway. Through comprehensive target deconvolution, a unique dual targeting mechanism was revealed. This work expands the chemical and druggable space of BMP modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Killian Oukoloff, Goodwell Nzou, Carmine Varricchio, Bobby Lucero, Thibault Alle, Jane Kovalevich, Ludovica Monti, Anne-Sophie Cornec, Yuemang Yao, Michael J. James, John Q. Trojanowski, Virginia M-Y Lee, Amos B. Smith, Andrea Brancale, Kurt R. Brunden, Carlo Ballatore
Summary: Triazolopyrimidines compounds show potential in treating Alzheimer's disease and neurodegenerative tauopathies, with the fragment at C6 playing a critical role in determining MT stability and integrity in cells. A new set of structurally modified analogues has been designed, synthesized, and evaluated, showing improved properties, activity, and pharmacokinetics compared to existing lead compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mounir A. A. Mohamed, Adnan A. Bekhit, Omyma A. Abd Allah, Asmaa M. Kadry, Tamer M. Ibrahim, Salma A. Bekhit, Kikuko Amagase, Ahmed M. M. El-Saghier
Summary: A series of novel [1,2,4]-triazole derivatives bearing amino acids were synthesized using lemon juice as an acidic catalyst under green chemistry conditions. These compounds showed promising antibacterial activity against standard bacteria and multidrug resistant strains, with better MIC values compared to reference drugs. Some compounds exhibited bacteriostatic activity and high selectivity towards antimicrobial activity against specific bacteria, indicating a good safety profile.
Article
Chemistry, Medicinal
Lin Chen, Tang-Yang Ji, Xian-Sen Huo, Zhi-Yu Zeng, Wei-Xuan Ye, Chen-Chen Dai, Yu-Qi Zhang, Wen-Wei You, Pei-Liang Zhao
Summary: A series of new compounds were designed and synthesized as potential tubulin polymerization inhibitors, among which one compound showed excellent antiproliferative activity and selectivity against cancer cells, as well as significant tubulin polymerization inhibitory activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Srinivas Reddy Merugu, Srinivasulu Cherukupalli, Rajshekhar Karpoormath
Summary: [1,2,4]Triazolo[1,5-a]pyrimidine is an important heterocyclic scaffold known for its broad range of pharmacological activities, and several marketed drugs have demonstrated its potential in medicinal chemistry. This review provides an overview of the synthetic strategies and pharmacological applications of differently substituted [1,2,4]triazolo[1,5-a]pyrimidine, with a focus on structure-activity relationship studies.
CHEMISTRY & BIODIVERSITY
(2022)
Article
Chemistry, Medicinal
Xian-Sen Huo, Xie-Er Jian, Jie Ou-Yang, Lin Chen, Fang Yang, Dong-Xin Lv, Wen-Wei You, Jin-Jun Rao, Pei-Liang Zhao
Summary: The novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives showed great potential as tubulin polymerization inhibitors, with high antiproliferative activity and selectivity against cancer cells. These compounds inhibit tumor cell growth by affecting the cell cycle, inducing apoptosis, and inhibiting tubulin polymerization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Engineering, Environmental
Hui Dou, Peng Chen, Lu Hu, Chunlin He, Siping Pang
Summary: Three neutral energetic compounds with a novel oxygen-containing fused ring were synthesized and fully characterized in this study. Their detonation performances were evaluated based on their decomposition temperature, density, and impact sensitivity.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Papisetti Venkatesham, Mansi Kalonia, Akanksha Ashok Sangolkar, Anwita Mudiraj, Phanithi Prakash Babu, Rajeswar Rao Vedula
Summary: A novel one-pot synthesis method for potential anticancer triazolopyrimidines was reported. The synthesized compounds showed concentration dependent inhibition against breast cancer cells, and one compound exhibited good binding interaction with amino acid residues in molecular docking simulation.
Article
Chemistry, Medicinal
Thibault Alle, Carmine Varricchio, Yuemang Yao, Bobby Lucero, Goodwell Nzou, Stefania Demuro, Megan Muench, Khoa D. Vuong, Killian Oukoloff, Anne-Sophie Cornec, Karol R. Francisco, Conor R. Caffrey, Virginia M. -Y. Lee, Amos B. Smith III, Andrea Brancale, Kurt R. Brunden, Carlo Ballatore
Summary: Researchers designed, synthesized, and evaluated a series of new triazolo[1,5-a]-pyrimidine compounds, and further elucidated the structure-activity relationships of these compounds through matched molecular pair analyses and computational studies. The study identified novel microtubule-stabilizing triazolo[1,5-a]-pyrimidine candidates that exhibited favorable ADME-PK properties, including brain penetration and oral bioavailability, as well as brain pharmacodynamic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Zihao Li, Kongxi Qiu, Xiao Yang, Wei Zhou, Qian Cai
Summary: A base-promoted tandem SNAr/Boulton-Katritzky rearrangement is developed for the formation of functionalized [1,2,4]triazolo[1,5-a]pyridines from 1,2,4-oxadiazol-3-amines or 3-aminoisoxazoles with 2-fluoropyridines.
Article
Chemistry, Organic
Jia Hui Ng, Anton Dolzhenko
Summary: A microwave-assisted method was developed for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines from 5-aminopyrazolyl-4-carbonitriles, orthoesters, and hydrazides in one pot. The method uses anisole as a green media and allows for diverse pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine preparation with variations in the structure of each substrate. The catalyst-free one-pot protocol, short reaction time, and convenient work-up are additional advantageous features of this method.
Article
Chemistry, Applied
Denis A. Gazizov, Alexander S. Steparuk, Nadezhda S. Demina, Ekaterina F. Zhilina, Oleg S. Eltsov, German S. Lebedkin, Gennady L. Rusinov, Alexey E. Alexandrov, Alexey R. Tameev
Summary: Novel [1,2,4]triazolo[1,5-a]pteridine derivatives were synthesized for the creation of test systems based on them. It was found that the substituent in the pyrazine ring of the TPt framework had a stronger influence on photophysical properties than that in the triazole ring. Although the fluorescence quantum yields of the compounds were generally low (3-23%), some of the TPt derivatives showed sensitivity to trace amounts of organic peroxides, making them promising for test systems. Additionally, the low-lying HOMO energy levels, energy gap values, and electron mobility of TPt materials suggest their potential use in organic electronic devices.
Article
Cell Biology
Emmanuel Heilmann, Francesco Costacurta, Seyed Arad Moghadasi, Chengjin Ye, Matteo Pavan, Davide Bassani, Andre Volland, Claudia Ascher, Alexander Kurt Hermann Weiss, David Bante, Reuben S. Harris, Stefano Moro, Bernhard Rupp, Luis Martinez-Sobrido, Dorothee von Laer
Summary: Protease inhibitors are effective antiviral drugs, and Nirmatrelvir is the first protease inhibitor developed specifically against the SARS-CoV-2 protease 3CLpro. By using a chimeric vesicular stomatitis virus (VSV), researchers identified mutations that confer resistance to nirmatrelvir.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Jason Mighty, Alfonso Rubio-Navarro, Cui Shi, Jing Zhou, Miguel Flores-Bellver, Soren Heissel, Onyekwere Onwumere, Linda Einbond, Rajendra Gharbaran, Daniel S. Casper, Alberto Benito-Martin, Stephen Redenti
Summary: Diabetic Retinopathy (DR) is a retinal disorder caused by diabetes. The lack of disease predictors makes the prognosis poor, leading to irreversible retinal damage and vision loss. Extracellular Vesicles (EVs) have the potential to be used as pre-symptomatic biomarkers for DR. EV proteins derived from urine may serve as noninvasive biomarkers.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Medicinal
Andrea Spinaci, Michela Buccioni, Daniela Catarzi, Chang Cui, Vittoria Colotta, Diego Dal Ben, Eleonora Cescon, Beatrice Francucci, Ilenia Grieco, Catia Lambertucci, Gabriella Marucci, Davide Bassani, Matteo Pavan, Flavia Varano, Stephanie Federico, Giampiero Spalluto, Stefano Moro, Rosaria Volpini
Summary: Through screening of a chemical library, a series of di- and tri-substituted adenine derivatives were synthesized and tested for their ability to inhibit the activity of CK1 delta and to bind ARs. The compound N-6-methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (17) showed the best balance of A(2A)AR affinity and CK1 delta inhibitory activity. Computational studies were performed to simulate the protein-ligand interactions. Therefore, compound 17 could be considered a lead compound for the treatment of chronic neurodegenerative and cancer diseases with synergistic effects.
Article
Chemistry, Medicinal
Teresa Gianferrara, Matteo Pavan, Davide Bassani, Fabrizio Vincenzi, Silvia Pasquini, Giovanni Bolcato, Katia Varani, Giampiero Spalluto, Stephanie Federico, Stefano Moro
Summary: Traditionally, molecular recognition between adenosine receptors and their ligands has been thought to occur with a 1:1 stoichiometry. However, recent simulations suggest an alternative 2:1 binding stoichiometry. In this study, a bis-ribosyl adenosine derivative, BRA1, was synthesized and tested for its binding and activation abilities on adenosine receptors, with molecular modeling used to rationalize its activity.
Article
Chemistry, Medicinal
Camilla Pecoraro, Michele De Franco, Daniela Carbone, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: Metabolic deregulation is a key mechanism in promoting cancer resistance and progression. In this study, novel hybrid molecules were synthesized and evaluated for their ability to inhibit PDK, resulting in the suppression of pancreatic cancer cell growth and spread. These compounds also showed promising results in animal models, reducing tumor growth without significant side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Silvia Menin, Matteo Pavan, Veronica Salmaso, Mattia Sturlese, Stefano Moro
Summary: Molecular docking is commonly used in rational drug design due to its rapid execution and accurate results. However, docking programs can sometimes have inaccuracies in scoring and ranking generated poses. To address this, researchers have proposed post-docking filters and refinement protocols, including pharmacophore models and molecular dynamics simulations. This study presents the application of Thermal Titration Molecular Dynamics (TTMD) to refine docking results by evaluating protein-ligand unbinding kinetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrea Dodaro, Matteo Pavan, Stefano Moro
Summary: The latest outbreak of monkeypox virus in 2022 highlights the potential threat it poses to public health. Due to the lack of specific treatments, the monkeypox virus I7L protease has been identified as a potential target for the development of new drugs. Through computational modeling and virtual screening, 14 potential inhibitors of the monkeypox I7L protease have been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela Carbone, Michele De Franco, Camilla Pecoraro, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: A library of 3-amino-1,2,4-triazine derivatives was designed and synthesized, which showed potent and selective inhibition of PDK. These compounds proved to be effective in inducing cancer cell death, especially in human pancreatic KRAS mutated cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Valentina Albanese, Sonia Missiroli, Mariasole Perrone, Martina Fabbri, Caterina Boncompagni, Salvatore Pacifico, Tiziano De Ventura, Antonella Ciancetta, Giulio Dondio, Franz Kricek, Paolo Pinton, Remo Guerrini, Delia Preti, Carlotta Giorgi
Summary: A series of aryl sulfonamide derivatives (ASDs) were designed and synthesized to inhibit the activation of the NLRP3 inflammasome. Compounds 6c, 7n, and 10 specifically inhibited NLRP3 activation at nanomolar concentrations without affecting the activation of other inflammasomes. These compounds were also found to reduce IL-1 beta production in vivo and attenuate melanoma tumor growth. The findings suggest that these potent NLRP3 inflammasome inhibitors could be considered for future therapeutic approaches in NLRP3 inflammasome-driven cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Stephanie Federico, Margherita Persico, Letizia Trevisan, Chiara Biasinutto, Giovanni Bolcato, Veronica Salmaso, Tatiana Da Ros, Teresa Gianferrara, Filippo Prencipe, Sonja Kachler, Karl-Norbert Klotz, Sabrina Pacor, Stefano Moro, Giampiero Spalluto
Summary: This study identified a new selective antagonist for the A(3) adenosine receptor, which showed pro-proliferative effects on cancer cells. These findings provide a foundation for further investigation of its mechanism and potential therapeutic applications.
Article
Biochemistry & Molecular Biology
Maria Chiara Scaini, Luisa Piccin, Davide Bassani, Antonio Scapinello, Stefania Pellegrini, Cristina Poggiana, Cristina Catoni, Debora Tonello, Jacopo Pigozzo, Luigi Dall'Olmo, Antonio Rosato, Stefano Moro, Vanna Chiarion-Sileni, Chiara Menin
Summary: The FDA has approved MAPK inhibitors for treating melanoma patients with BRAF gene mutation in the V600 codon. However, rare BRAF mutations outside the V600 codon may also cause melanoma, and their response to BRAF inhibitor treatment is still not well understood. In this study, a patient with a rare p.T599dup B-RAF mutation was found to have a good response to Dabrafenib/Trametinib targeted therapy. In-silico modeling showed that Dabrafenib could effectively bind to this rare mutation, suggesting the possibility of broadening the spectrum of BRAF inhibitor-sensitive mutations beyond the V600 codon.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Veronica Salmaso, Margherita Persico, Tatiana Da Ros, Giampiero Spalluto, Sonja Kachler, Karl-Norbert Klotz, Stefano Moro, Stephanie Federico
Summary: This study investigates the structural features of ligands leading to affinity and/or selectivity at adenosine receptors. The findings suggest that bulky acyl moieties at position N5 and small alkyl groups at position N8 are associated with affinity and selectivity at the A(3) receptor. Meanwhile, a free amino function at the 5 position induces high affinity at the A(2A) and A(1) receptors.
