Article
Biochemistry & Molecular Biology
Clemens Hinteregger, Johanna Dolensky, Werner Seebacher, Robert Saf, Pascal Maeser, Marcel Kaiser, Robert Weis
Summary: 2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes have activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against malaria tropica and sleeping sickness pathogens. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as the position of the nitrogen atom in the bicycles.
Article
Chemistry, Medicinal
Mohammad-Reza Delnavazi, Samad Nejad Ebrahimi, Abbas Hadjiakhoondi, Narguess Yassa
Summary: Seven undescribed sesquiterpene derivatives, Azerins A-G (3-6, 8, 14 and 15), along with known sesquiterpene phenols (1, 2 and 7) and sesquiterpene coumarins (9-13), were isolated from the roots of Dorema glabrum. Their structures were determined using NMR and MS techniques. The compounds were evaluated for their antiprotozoal and cytotoxic activities, and Azerin G (15) exhibited potent growth inhibitory activity against T. b. rhodesiense, while compounds 1, 4, 7, and 8 showed selective inhibitory effects on P. falciparum.
Review
Biochemistry & Molecular Biology
Antonio Moreno-Herrera, Sandra Cortez-Maya, Virgilio Bocanegra-Garcia, Bimal Krishna Banik, Gildardo Rivera
Summary: Parasitic infections caused by various protozoa affect millions of people worldwide annually, with limited pharmacological treatments. Developing new and more effective drugs could be crucial in improving therapy outcomes for parasitic diseases.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Alexandra Ibanez-Escribano, Cristina Fonseca-Berzal, Monica Martinez-Montiel, Manuel Alvarez-Marquez, Maria Gomez-Nunez, Manuel Lacueva-Arnedo, Teresa Espinosa-Buitrago, Tania Martin-Perez, Jose Antonio Escario, Penelope Merino-Montiel, Sara Montiel-Smith, Alicia Gomez-Barrio, Oscar Lopez, Jose G. Fernandez-Bolanos
Summary: In this study, a series of antiprotozoal compounds were synthesized by modifying the substituents on N-1 and N-4 and the nature of the chalcogen atom. The compounds showed good activity against Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 exhibited the best trypanocidal activity, while thiosemicarbazones 49, 51, and 63 showed remarkable trichomonacidal effects. The compounds were also found to be non-toxic to mammalian cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yang Zheng, Magali van den Kerkhof, Tiffany van der Meer, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Iwan J. P. de Esch, Marco Siderius, An Matheeussen, Louis Maes, Geert Jan Sterk, Guy Caljon, Rob Leurs
Summary: The discovery of 5-phenylpyrazolopyrimidinone analogs as a novel series of antitrypanosomal agents shows promise for developing new medications to treat Human African Trypanosomiasis (HAT). The most potent compound, 30, has a low toxicity potential and exhibits high in vitro and in vivo antitrypanosomal activity against T. b. brucei.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Colm P. Roster, Danielle Lavigne, Jillian E. Milanes, Emily Knight, Heidi D. Anderson, Sabrina Pizarro, Elijah M. Harding, Meredith T. Morris, Victoria C. Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C. Rees, Brian Dominy, Daniel C. Whitehead, Md Nasir Uddin, Steven W. Millward, James C. Morris
Summary: Glucose metabolism is critical for the survival of Trypanosoma brucei, and inhibitors of human enolase have been found to be effective against the parasite.
Article
Plant Sciences
Barbara Verena Dias Galvao, Carlos Fernando Araujo-Lima, Monica Cristine Pereira dos Santos, Mariana Pulmar Seljan, Eduardo Kennedy Carrao-Dantas, Claudia Alessandra Fortes Aiub, Luiz Claudio Cameron, Mariana Simoes Larraz Ferreira, Edira Castello Branco de Andrade Goncalves, Israel Felzenszwalb
Summary: The study identified 14 phenolic compounds in Plinia cauliflora leaf extract, showing certain anti-Trypanosoma cruzi activity but also cytotoxic effects on liver cell lines.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Roberto Docampo, Anibal Eugenio Vercesi
Summary: This review discusses the mechanisms of mitochondrial oxidant generation and removal, and the involvement of Ca2+ in trypanosome cell death, highlighting the need for further studies on ROS generation, defense mechanisms, and mitochondrial permeability transition pore in trypanosomatids.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Multidisciplinary Sciences
Justin Y. Toh, Agathe Nkouawa, Saul Rojas Sanchez, Huafang Shi, Nikolay G. Kolev, Christian Tschudi
Summary: By targeting 86 transcripts through RNAi, 22 genes that positively or negatively regulate the progression towards infectivity in Trypanosoma brucei have been identified, including the previously unknown nucleic acid binding proteins CSD1 and CSD2. The study suggests a considerable overlap between the genes that regulate stumpy bloodstream form Trypanosoma and those that govern the development of metacyclic form parasites.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Nava Raj Poudyal, Kimberly S. Paul
Summary: This review discusses the availability and uptake mechanisms of fatty acids in Trypanosoma brucei. Fatty acids can be synthesized by the parasite or acquired from the host's surroundings. Fatty acids are crucial for the growth and survival of the parasite and are implicated in the survival of specific proteins. The relative contribution of parasite-derived and host-derived fatty acids to T. brucei biology and the molecular mechanisms of fatty acid uptake are still poorly understood.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Jens C. Lindhof, Irina Ihnatenko, Marco J. Mueller, Oliver C. F. Orban, Cecilia Ortiz, Diego Benitez, Estefania Dibello, Leonardo L. Seidl, Marcelo A. Comini, Conrad Kunick
Summary: Parasitic kinetoplastid diseases pose serious threats to populations in the (sub-)tropics. Current drugs lack proper properties, requiring the urgent need for new candidates. Through molecular simplification and ring disconnection approaches, we identified new compounds with improved potency and selectivity against the target enzyme.
Article
Immunology
Manon Geerts, Nick Van Reet, Sander Leyten, Raf Berghmans, Kat S. Rock, Theresa H. T. Coetzer, Lauren E-A Eyssen, Philippe Buscher
Summary: The newly developed T. b. gambiense inhibition ELISA (g-iELISA) based on the principle of antibody binding showed high specificity and sensitivity, making it suitable for regional laboratories in gHAT endemic countries for monitoring and surveillance.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Johanna Dolensky, Clemens Hinteregger, Andreas Leitner, Werner Seebacher, Robert Saf, Ferdinand Belaj, Pascal Maser, Marcel Kaiser, Robert Weis
Summary: N-(Aminoalkyl)azabicyclo[3.2.2]nonanes with terminal tetrazole or sulfonamido partial structure were synthesized. The structures of these compounds were confirmed by various analyses. In vitro experiments showed that the sulfonamide and tetrazole derivatives exhibited significant activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense.
Review
Chemistry, Medicinal
Harsh S. Amin, Palak K. Parikh, Manjunath D. Ghate
Summary: PDE10A is highly expressed in the brain, regulating cyclic nucleotide signaling. PDE10A inhibitors are expected to be a new approach for treating schizophrenia and other neurodegenerative disorders, with pharmaceutical companies conducting research and development in this area.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Samya S. Alenezi, Naif D. Alenezi, Godwin U. Ebiloma, Manal J. Natto, Marzuq A. Ungogo, John O. Igoli, Valerie A. Ferro, Alexander I. Gray, James Fearnley, Harry P. de Koning, David G. Watson
Summary: Profiling of a propolis sample from Papua New Guinea revealed the presence of several triterpenoids, which exhibited moderate to high activity against parasitic protozoa but low cytotoxicity against mammalian cells.
Article
Biochemical Research Methods
Helena Balabin, Charles Tapley Hoyt, Colin Birkenbihl, Benjamin M. Gyori, John Bachman, Alpha Tom Kodamullil, Paul G. Ploeger, Martin Hofmann-Apitius, Daniel Domingo-Fernandez
Summary: In this study, a multimodal model called STonKGs, based on Transformer, is proposed to generate better representations of biological knowledge by combining knowledge graphs and biomedical text data. The results demonstrate that STonKGs outperforms baseline models in various classification tasks and can be adapted to other transfer learning applications.
Article
Biochemical Research Methods
Oezlem Muslu, Charles Tapley Hoyt, Mauricio Lacerda, Martin Hofmann-Apitius, Holger Froehlich
Summary: The study proposes a novel approach, GuiltyTargets, for prioritization of putative targets using attributed network representation learning and positive-unlabeled learning. The evaluation on multiple disease datasets demonstrates its superiority over previous methods and its potential for target repositioning across related diseases.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Article
Biochemical Research Methods
Sara Mohammad-Taheri, Jeremy Zucker, Charles Tapley Hoyt, Karen Sachs, Vartika Tewari, Robert Ness, Olga Vitek
Summary: This article proposes a general and practical approach for estimating causal queries based on latent variable models. It proves the accuracy of the approach under specific conditions and demonstrates its broad applicability and practicality through synthetic and experimental case studies.
Correction
Chemistry, Medicinal
Antonino Nicoloo Fallica, Carla Barbaraci, Emanuele Amata, Lorella Pasquinucci, Rita Turnaturi, Maria Dichiara, Sebastiano Intagliata, Marzia Bruna Gariboldi, Emanuela Marras, Viviana Teresa Orlandi, Claudia Ferroni, Cecilia Martini, Antonio Rescifina, Davide Gentile, Greta Varchi, Agostino Marrazzo
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Rita Turnaturi, Santina Chiechio, Lorella Pasquinucci, Salvatore Spoto, Giuliana Costanzo, Maria Dichiara, Silvia Piana, Margherita Grasso, Emanuele Amata, Agostino Marrazzo, Carmela Parenti
Summary: Although opioids and NSAIDs have many side effects, the development of new analgesics and the investigation of new mechanisms provide promising alternatives for persistent pain treatment.
Article
Biology
Laura M. Doherty, Caitlin E. Mills, Sarah A. Boswell, Xiaoxi Liu, Charles Tapley Hoyt, Benjamin Gyori, Sara J. Buhrlage, Peter K. Sorger, Silke Hauf
Summary: This study establishes a knowledgebase of DUB activities, co-dependent genes, and substrates, utilizing targeted experiments and systematic mining of functional genomic databases. The findings provide insights into the important role of DUBs in regulating cellular activities and suggest their potential as therapeutic targets for cancer and other diseases.
Review
Biochemical Research Methods
Stephen Bonner, Ian P. Barrett, Cheng Ye, Rowan Swiers, Ola Engkvist, Andreas Bender, Charles Tapley Hoyt, William L. Hamilton
Summary: This review provides a detailed introduction to publicly available data sources suitable for constructing drug discovery focused knowledge graphs (KGs). It aims to guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field but may lack knowledge of relevant data sources. The review includes a comparative analysis of existing public drug discovery KGs, evaluation of motivating case studies, and raises challenges and future research directions in the domain. It hopes to motivate the use of KGs in addressing key and emerging questions in drug discovery.
BRIEFINGS IN BIOINFORMATICS
(2022)
Editorial Material
Chemistry, Medicinal
Maria Dichiara, Emanuele Amata
Summary: Integrating efforts from pharmacologists and biologists into sustained innovation from synthetic chemists is crucial for the progress of H2S research and the development of H2S therapeutics for clinical use.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Computer Science, Artificial Intelligence
Mehdi Ali, Max Berrendorf, Charles Tapley Hoyt, Laurent Vermue, Mikhail Galkin, Sahand Sharifzadeh, Asja Fischer, Volker Tresp, Jens Lehmann
Summary: This study re-implemented and evaluated 21 knowledge graph embedding models and performed large-scale benchmarking to assess the reproducibility of previously published results. The results highlight that a model's performance is determined by multiple factors, not just its architecture. The study provides insights into best practices and configurations, as well as suggestions for further improvements.
IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE
(2022)
Article
Multidisciplinary Sciences
Charles Tapley Hoyt, Meghan Balk, Tiffany J. Callahan, Daniel Domingo-Fernandez, Melissa A. Haendel, Harshad B. Hegde, Daniel S. Himmelstein, Klas Karis, John Kunze, Tiago Lubiana, Nicolas Matentzoglu, Julie McMurry, Sierra Moxon, Christopher J. Mungall, Adriano Rutz, Deepak R. Unni, Egon Willighagen, Donald Winston, Benjamin M. Gyori
Summary: The standardized identification of biomedical entities is important for interoperability and data integration in the life sciences. The Bioregistry is an integrative and open metaregistry that expands upon existing registries to address the evolving needs of researchers. By leveraging public infrastructure and automation, and employing an open code and open data governance model, the Bioregistry promotes interoperability and reuse of data and scientific literature.
Article
Philosophy
Luca Settimo
Summary: Throughout his career, Hans Jonas has reflected on the notion of the human soul and on the concept of man being created in God's image. From 1968, he changed his perspective on these topics, emphasizing the importance of the Judeo-Christian notion of imago Dei for his ethical project. He used this concept to show the special role assigned to humanity as a steward of God's creation.
HISTORY OF EUROPEAN IDEAS
(2023)
Article
Mathematical & Computational Biology
Nicolas Matentzoglu, Damien Goutte-Gattat, Shawn Zheng Kai Tan, James P. Balhoff, Seth Carbon, Anita R. Caron, William D. Duncan, Joe E. Flack, Melissa Haendel, Nomi L. Harris, William R. Hogan, Charles Tapley Hoyt, Rebecca C. Jackson, HyeongSik Kim, Huseyin Kir, Martin Larralde, Julie A. McMurry, James A. Overton, Bjoern Peters, Clare Pilgrim, Ray Stefancsik, Sofia M. C. Robb, Sabrina Toro, Nicole A. Vasilevsky, Ramona Walls, Christopher J. Mungall, David Osumi-Sutherland
Summary: This article discusses the complex workflows involved in managing the ontology life cycle and the diverse set of tools required for this process. Standardizing release practices and quality standards are crucial in the biomedical domain to enable interoperability. The article also provides an overview of the Ontology Development Kit (ODK) and its practical applications.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2022)
Article
Mathematical & Computational Biology
Nicolas Matentzoglu, James P. Balhoff, Susan M. Bello, Chris Bizon, Matthew Brush, Tiffany J. Callahan, Christopher G. Chute, William D. Duncan, Chris T. Evelo, Davera Gabriel, John Graybeal, Alasdair Gray, Benjamin M. Gyori, Melissa Haendel, Henriette Harmse, Nomi L. Harris, Ian Harrow, Harshad B. Hegde, Amelia L. Hoyt, Charles T. Hoyt, Dazhi Jiao, Ernesto Jimenez-Ruiz, Simon Jupp, Hyeongsik Kim, Sebastian Koehler, Thomas Liener, Qinqin Long, James Malone, James A. McLaughlin, Julie A. McMurry, Sierra Moxon, Monica C. Munoz-Torres, David Osumi-Sutherland, James A. Overton, Bjoern Peters, Tim Putman, Nuria Queralt-Rosinach, Kent Shefchek, Harold Solbrig, Anne Thessen, Tania Tudorache, Nicole Vasilevsky, Alex H. Wagner, Christopher J. Mungall
Summary: This paper introduces the "Simple Standard for Sharing Ontological Mappings (SSSOM)" standard, which addresses issues in mapping different representations of objects in different databases by enhancing readability of metadata, defining an easy-to-use table-based format, and implementing open collaborative workflows. The standard provides reference tools and software libraries for handling mappings.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2022)
Review
Computer Science, Artificial Intelligence
Jeremy Leipzig, Daniel Nuest, Charles Tapley Hoyt, Karthik Ram, Jane Greenberg
Summary: This article discusses how metadata standards supporting reproducibility play a role in the analytic stack, identifying gaps and trends for future work. Recommendations are provided for improving reproducible computational research.
Correction
Chemistry, Medicinal
Antonino Nicoloo Fallica, Carla Barbaraci, Emanuele Amata, Lorella Pasquinucci, Rita Turnaturi, Maria Dichiara, Sebastiano Intagliata, Marzia Bruna Gariboldi, Emanuela Marras, Viviana Teresa Orlandi, Claudia Ferroni, Cecilia Martini, Antonio Rescifina, Davide Gentile, Greta Varchi, Agostino Marrazzo
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
