Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Agni F. M. Gavriilidou, Kleitos Sokratous, Hsin-Yung Yen, Luigi De Colibus
Summary: Studying protein-ligand interactions can greatly assist in the design of new therapeutic molecules. Various techniques used in drug discovery, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, rely on protein crystallography and cryo-electron microscopy. Native mass spectrometry is a versatile method for studying proteins and their interactions, providing valuable insights into protein structure and thermodynamics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Manish Kothakonda, Yanglin Zhu, Yingdong Guan, Jingyang He, Jamin Kidd, Ruiqi Zhang, Jinliang Ning, Venkatraman Gopalan, Weiwei Xie, Zhiqiang Mao, Jianwei Sun
Summary: Recent advances in 2D magnetism have led to increased interest in layered magnetic materials for spintronics applications. Layered semiconducting antiferromagnets exhibit unique low-dimensional semiconducting behavior and can be controlled by both charge and spin. However, synthesizing these compounds is challenging and rare. In this study, a high-throughput search based on first-principles was conducted to identify potentially stable mixed metal phosphorus trichalcogenides. Among the candidates, a stable semiconducting layered magnetic material, CdFeP2Se6, was successfully synthesized, exhibiting short-range antiferromagnetic order at 21 K with an indirect bandgap of 2.23 eV. This work suggests that high-throughput screening-assisted synthesis can be an effective method for discovering layered magnetic materials.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Immunology
Julian Ernesto Nicolas Gulin, Margarita Maria Catalina Bisio, Daniela Rocco, Jaime Altcheh, Maria Elisa Solana, Facundo Garcia-Bournissen
Summary: This study evaluates the efficacy of Miltefosine (MLT) as a monodrug and combined with benznidazole (BZ) for treating Trypanosoma cruzi infection. MLT showed promising results in inhibiting the parasite in both in vitro and in vivo models, with improved efficacy when combined with BZ. This study provides support for the potential use of MLT in Chagas disease treatment and the exploration of combination therapies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ruben Martin-Escolano, Daniel Molina-Carreno, Javier Martin-Escolano, M. Paz Clares, Cristina Galiana-Rosello, Jorge Gonzalez-Garcia, Nuria Cirauqui, Jose M. Llinares, Maria Jose Rosales, Enrique Garcia-Espana, Clotilde Marin
Summary: Chagas disease, caused by Trypanosoma cruzi, is a potentially fatal infection that was previously limited to Latin America but has now become widespread globally. This study identified new effective agents against T. cruzi and evaluated their efficacy in vivo. Compound 15 was identified as a potential candidate for the development of new therapies for Chagas disease.
Article
Multidisciplinary Sciences
Iwona Grad, Robert Hanes, Pilar Ayuda-Duran, Marieke Lydia Kuijjer, Jorrit M. Enserink, Leonardo A. Meza-Zepeda, Ola Myklebost
Summary: Drug testing on liposarcoma cells has identified six potential anti-cancer drugs that target different mechanisms and have low toxicity to normal cells. These drugs show promise for the treatment of liposarcoma.
Article
Chemistry, Multidisciplinary
Zihan Yang, Zhihang Zhou, Tongxu Si, Zhengdong Zhou, Li Zhou, Y. Rebecca Chin, Liang Zhang, Xinyuan Guan, Mengsu Yang
Summary: Cancer metastasis is a major cause of cancer-related death, and it is characterized by excessive extracellular matrix deposition and increased stiffness in solid tumors. The confined migration of tumor cells in these conditions plays a crucial role in metastasis, but inhibitors specifically targeting this type of migration are rare. In this study, a microfluidic chip was designed to screen for drugs that can effectively inhibit confined migration of cancer cells. By applying this chip, three novel inhibitors of confined migration, MA-5, SB-705498, and diphenyleneiodonium chloride, were discovered in multiple cancer types. The mechanisms of action of these inhibitors were found to be targeting mitochondria, actin polymerization, and cell viability, respectively. Overall, a high-throughput microfluidic platform for screening drugs targeting confined migration was established, and three effective inhibitors were identified.
Article
Biochemistry & Molecular Biology
Michael J. da Silva, Andrey P. Jacomini, Davana S. Goncalves, Karlos Eduardo Pianoski, Julia Poletto, Danielle Lazarin-Bidoia, Helito Volpato, Celso Nakamura, Fernanda A. Rosa
Summary: A novel tetrasubstituted pyrazole derivative was discovered to exhibit potent and selective inhibition against both L. amazonensis and T. cruzi, offering a new approach for the treatment of Chagas disease and Leishmaniasis.
BIOORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Ningning Tang, Ling Li, Fei Xie, Ying Lu, Zifan Zuo, Hao Shan, Quan Zhang, Lianwen Zhang
Summary: Inhibition of cellular O-GlcNAcylation can suppress proliferation and migration of cancer cells, leading to a new avenue for cancer therapy. A cell-based fluorescent reporter was developed to sense changes in cellular O-GlcNAcylation, allowing for identification of natural compounds such as sesamin that inhibit O-GlcNAcylation and migration of cancer cells.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Review
Biotechnology & Applied Microbiology
Hasan Aldewachi, Radhwan N. Al-Zidan, Matthew T. Conner, Mootaz M. Salman
Summary: Neurodegenerative diseases are incurable conditions that cause progressive degeneration or death of nerve cells. Identifying therapeutic targets and new treatments is a major challenge, and high-throughput screening plays a key role in improving drug discovery efficiency.
BIOENGINEERING-BASEL
(2021)
Article
Multidisciplinary Sciences
Priyanka Parijat, Saraswathi Ponnam, Seetharamaiah Attili, Kenneth S. Campbell, Mohammed El-Mezgueldi, Mark Pfuhl, Thomas Kampourakis
Summary: The unmet demand for new heart failure therapeutics is well recognized and targeting the contractile myofilaments has shown potential for the development of new drugs. However, limited clinical use and incomplete understanding of myofilament function have hindered progress in this area. In this study, new high throughput screening platforms were designed and validated to explore the effects of small molecule effectors on the interactions between cardiac troponin C and troponin I subunits. The results suggest that sarcomeric protein-directed screening platforms are suitable for developing compounds that modulate cardiac myofilament function.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Marko Jukic, Rodolphe Auger, Victor Folcher, Matic Proj, Helene Barreteau, Stanislav Gobec, Thierry Touze
Summary: The study identified small molecules that inhibit the activity of BacA, an enzyme involved in the recycling of undecaprenyl pyrophosphate. The compounds showed significant inhibition of the enzyme's activity and also demonstrated antibacterial activity against Escherichia coli strains.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Virology
Rafaela Sachetto Fernandes, Andre Schutzer de Godoy, Igor Andrade Santos, Gabriela Dias Noske, Ketllyn Irene Zagato de Oliveira, Victor Oliveira Gawriljuk, Ana Carolina Gomes Jardim, Glaucius Oliva
Summary: The 2015/16 Zika virus epidemic caused nearly 1 million confirmed cases in 84 countries and was associated with congenital microcephaly and Guillain-Barre syndrome. A ZIKV replicon cell line was developed and characterized for screening viral replication inhibitors. Two molecules with potent anti-ZIKV activities were identified through this replicon-based cell system, showing potential for antiviral drug discovery.
Article
Chemistry, Physical
Byung Chul Yeo, Hyunji Nam, Hyobin Nam, Min-Cheol Kim, Hong Woo Lee, Sung-Chul Kim, Sung Ok Won, Donghun Kim, Kwan-Young Lee, Seung Yong Lee, Sang Soo Han
Summary: The study introduces a high-throughput screening protocol for discovering alternative catalysts to palladium, identifying a previously unreported bimetallic catalyst with enhanced performance and productivity.
NPJ COMPUTATIONAL MATERIALS
(2021)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Infectious Diseases
Irene Losada Galvan, Julio Alonso-Padilla, Nuria Cortes-Serra, Cristina Alonso-Vega, Joaquim Gascon, Maria Jesus Pinazo
Summary: The text emphasizes the importance of benznidazole as a treatment for Chagas disease and its potential future use with different treatment schemes. Chemical, pharmacokinetic, and pharmacodynamic structures are discussed, along with data from previous studies and ongoing research. Other topics covered include indications for treatment, challenges such as adverse effects and access barriers, and alternative strategies to improve treatment access and safety.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Article
Chemistry, Medicinal
Soledad Natalia Gonzalez, Jonathan J. Mills, Dante Maugeri, Christopher Olaya, Breana L. Laguera, Jeffrey R. Enders, Julian Sherman, Ana Rodriguez, Joshua G. Pierce, Juan Jose Cazzulo, Edward L. D'Antonio
Summary: The study discovered a competitive inhibitor Compound B targeting ribose 5-phosphate isomerase type B (RPI-B), which exhibited significant trypanocidal activity against T. cruzi infective life-stages. By targeting the active site residue Cys-69, this inhibitor provided a proof-of-concept for the development of next generation inhibitors with potential prodrug groups to treat Chagas' disease in the future.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Nieves Martinez-Peinado, Clara Martori, Nuria Cortes-Serra, Julian Sherman, Ana Rodriguez, Joaquim Gascon, Jordi Alberola, Maria-Jesus Pinazo, Alheli Rodriguez-Cortes, Julio Alonso-Padilla
Summary: The study found that 17-DMAG has a strong inhibitory effect on T. cruzi, particularly during the intracellular replicative stage of the parasite. Molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. However, evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting challenges in transitioning from in vitro assays to preclinical drug development stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pathology
Diana P. Wehrendt, Julio Alonso-Padilla, Bo Liu, Lizeth Rojas Panozo, Silvia Rivera Nina, Lilian Pinto, Daniel Lozano, Albert Picado, Marcelo Abril, Maria J. Pinazo, Joaquim Gascon, Faustino Torrico, Season Wong, Alejandro G. Schijman
Summary: Vertical transmission of Trypanosoma cruzi causes congenital Chagas disease, which requires early diagnosis and treatment. A LAMP technology coupled with automated DNA extraction device showed promise for point-of-care early diagnosis, with high sensitivity and specificity compared to traditional microscopy-based methods.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2021)
Article
Microbiology
Nieves Martinez-Peinado, Nuria Cortes-Serra, Julian Sherman, Ana Rodriguez, Juan M. Bustamante, Joaquim Gascon, Maria-Jesus Pinazo, Julio Alonso-Padilla
Summary: Chagas disease, caused by the parasite Trypanosoma cruzi, has its greatest burden in Latin America. Existing treatments present toxicity and variable efficacy, highlighting the urgent need for new therapeutic strategies. Drug repositioning offers a fast and low-cost approach to identify safer and more effective chemotherapies for Chagas disease.
Article
Chemistry, Medicinal
Scott B. Green, Robert J. Lanier Jr, Shane M. Carey, David R. Morgan, Hanna Gracz, Julian Sherman, Ana Rodriguez, Edward L. D'Antonio
Summary: The screening of eighteen amino sugar analogues against Trypanosoma cruzi glucokinase revealed five on-target confirmed inhibitors, all from the D-GlcN series. Four of these compounds were identified as strong TcGlcK inhibitors, while three showed significant in vitro anti-T. cruzi activity. Compounds 5 and 6 were further evaluated biochemically, with formal Ki values determined and exhibiting competitive inhibition mode for TcGlcK.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Letter
Respiratory System
Marisol Zuniga, Claudia Gomes, Steven E. Carsons, Michael T. Bender, Paolo Cotzia, Qing Robert Miao, David C. Lee, Ana Rodriguez
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Infectious Diseases
Juan Rivera-Correa, Joseph Verdi, Julian Sherman, Jeremy M. Sternberg, Jayne Raper, Ana Rodriguez
Summary: The study found evidence of autoimmunity against phosphatidylserine in Trypanosoma brucei infected mice and Human African Trypanosomiasis patients, suggesting a potential link between autoimmunity and anemia.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Plant Sciences
Nieves Martinez-Peinado, Javier E. Ortiz, Maria Jesus Pinazo, Joaquim Gascon, Alejandro Tapia, German Roitman, Jaume Bastida, Gabriela E. Feresin, Julio Alonso-Padilla
Summary: This study identified alkaloids with anti-T. cruzi activity from Habranthus brachyandrus collected in Argentina. The alkaloid ismine showed specific activity against the parasite and low toxicity against liver cells. These findings provide a new direction for the development of drugs for Chagas disease.
Article
Food Science & Technology
Albert Ros-Lucas, Pascal Bigey, Jean-Philippe Chippaux, Joaquim Gascon, Julio Alonso-Padilla
Summary: Snakebite envenomation causes a significant number of deaths each year, and the production of antivenoms is often limited by their variable potency and accessibility. This study presents a method based on sequence conservation and protein structural features to prioritize therapeutic epitopes from snake venom. The selected epitopes are applicable to the most medically important snake species in West Sub-Saharan Africa and can be customized for venom sequence analysis in other regions.
Article
Biochemistry & Molecular Biology
Alba L. Montoya, Elisa G. Carvajal, Uriel Ortega-Rodriguez, Igor L. Estevao, Roger A. Ashmus, Sohan R. Jankuru, Susana Portillo, Cameron C. Ellis, Colin D. Knight, Julio Alonso-Padilla, Luis Izquierdo, Maria-Jesus Pinazo, Joaquim Gascon, Veronica Suarez, Douglas M. Watts, Iliana R. Malo, Janine M. Ramsey, Belkisyole Alarcon De Noya, Oscar Noya, Igor C. Almeida, Katja Michael
Summary: Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people worldwide. The diagnosis and treatment assessment of Chagas disease is challenging due to parasite diversity and the lack of biomarkers. This study explores the potential of glycosylphosphatidylinositol-anchored mucins as biomarkers for diagnosis and treatment assessment in Chagas disease patients.
Article
Microbiology
Nieves Martinez-Peinado, Juan Carlos Gabaldon-Figueira, Ignacio Martinez-Anon, Cristian Rodriguez-Gordo, Raquel Robleda-Castillo, Maria-Jesus Pinazo, Pascal Bigey, Joaquim Gascon, Julio Alonso-Padilla
Summary: The serum parasite inhibition assay is a valuable tool for evaluating changes in Trypanosoma cruzi infection by exposing infective trypomastigotes to serum samples from infected patients. There is a clear correlation between the reactivity of the samples to the whole-parasite lysates by ELISA and the inhibitory effect. This study confirms the importance of the assay for measuring antibody efficacy.
Article
Plant Sciences
Javier E. Ortiz, Mauricio Pineiro, Nieves Martinez-Peinado, Patricia Barrera, Miguel Sosa, Jaume Bastida, Julio Alonso-Padilla, Gabriela E. Feresin
Summary: This study evaluated the anti-T. cruzi activity of the alkaloid candimine isolated from a plant, and assessed its combination effect with benznidazole, an existing drug. The results showed that candimine exhibited high anti-parasitic activity, and its combination with benznidazole enhanced its efficacy against T. cruzi, suggesting its potential as a new therapy for Chagas disease.
Article
Medicine, Research & Experimental
Claudia Gomes, Rosauro Varo, Miquel Duran-Frigola, Antonio Sitoe, Rubio Bila, Sonia Machevo, Alfredo Mayor, Quique Bassat, Ana Rodriguez
Summary: Malaria can progress from an uncomplicated infection to a life-threatening severe disease. Early symptoms are often nonspecific, making it difficult to identify patients at high risk. By analyzing the transcriptomic response of human brain microvascular endothelial cells to Plasmodium falciparum-infected erythrocytes, several biomarkers have been identified to distinguish uncomplicated from severe malaria, as well as to differentiate children with cerebral malaria within the severe malaria group.