Article
Pharmacology & Pharmacy
Leonardo da Silva Lara, Guilherme Curty Lechuga, Lorraine Martins Rocha Orlando, Byanca Silva Ferreira, Bernardo Araujo Souto, Mauricio Silva dos Santos, Mirian Claudia de Souza Pereira
Summary: Chagas disease is a long-standing disease that primarily affects impoverished populations in Latin America. The available drugs have limited effectiveness and intense side effects. This study explores the biological activity of two new series of pyrazole-thiazoline derivatives with potential therapeutic options against Trypanosoma cruzi. These derivatives show potent activity with good oral bioavailability and low cytotoxicity, making them potential candidates for Chagas disease therapy.
Article
Biochemistry & Molecular Biology
Pablo Igor Ribeiro Franco, Jose Rodrigues do Carmo Neto, Marina Pacheco Miguel, Juliana Reis Machado, Mara Rubia Nunes Celes
Summary: This review summarizes the main molecular mechanisms of T. cruzi-related carcinogenesis and the mechanisms associated with tumor protection mediated by different parasite components.
Article
Genetics & Heredity
Hans Desale, Pierre Buekens, Jackeline Alger, Maria Luisa Cafferata, Emily Wheeler Harville, Claudia Herrera, Carine Truyens, Eric Dumonteil
Summary: The study assessed the epigenetic effects of in utero exposure to maternal Trypanosoma cruzi infection. By comparing the DNA methylation patterns of umbilical cord blood cells from uninfected babies with chagasic and uninfected mothers, a differential DNA methylation signature was identified. The genes affected are related to hematopoietic cell differentiation, immune response, and developmental disorders.
Article
Immunology
Laura Fraccaroli, Maria Daniela Ruiz, Virginia Gabriela Perdomo, Agustina Nicole Clausi, Dario Emmanuel Balcazar, Luciana Larocca, Carolina Carrillo
Summary: "Chagas disease is an endemic American parasitosis caused by Trypanosoma cruzi. Current therapies have limited efficacy and side effects, leading to the need for new trypanocidal strategies. Ivermectin shows potential as a repurposed drug for Chagas disease, with dose-dependent effects on T. cruzi and other trypanosomatids, and potential novel molecular targets identified in this study."
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biology
Lorraine Martins Rocha Orlando, Leonardo da Silva Lara, Guilherme Curty Lechuga, Giseli Capaci Rodrigues, Omar Ginoble Pandoli, Druval Santos de Sa, Mirian Claudia de Souza Pereira
Summary: Therapeutic alternatives for Chagas disease are urgently needed due to limitations and adverse effects of current drugs. Triazole analogues show promise in treating T. cruzi.
Article
Biochemistry & Molecular Biology
Naiara Dutra Barroso Gomes, Emanuel Paula Magalhaes, Lyanna Rodrigues Ribeiro, John Washington Cavalcante, Marcelo Morais Gomes Maia, Felipe Ramon Cunha da Silva, Arif Ali, Marcia Machado Marinho, Emmanuel Silva Marinho, Helcio Silva dos Santos, Alice Maria Costa Martins, Ramon Roseo Paula Pessoa Bezerra de Menezes
Summary: This study evaluated the activity of synthetic p-aminochalcones against T. cruzi and found that they have a trypanocidal effect by causing membrane damage and oxidative stress. Their mechanism of action may be related to inhibition of cruzain and TR.
BIOORGANIC CHEMISTRY
(2023)
Article
Parasitology
Ruben Martin-Escolano, Maria Jose Rosales, Clotilde Marin
Summary: The T. cruzi Arequipa strain is characterized and evaluated as a model for drug discovery in Chagas disease. The study provides insights into the infection characteristics and benznidazole susceptibility of this strain, suggesting its potential for screening new compounds with anti-parasitic properties.
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
Biochemistry & Molecular Biology
Fanny E. Eberhard, Sven Klimpel, Alessandra A. Guarneri, Nicholas J. Tobias
Summary: The study aimed to detect differences in the intestinal metabolome of the triatomine Rhodnius prolixus and predict exposure status to T. cruzi with high accuracies using logistic regression, a random forest classifier and a gradient boosting machine model. Important features for predicting exposure status and major metabolites for positive classification were identified, highlighting the complex interactions between triatomine vectors and parasites.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Immunology
Albert Ros-Lucas, Nieves Martinez-Peinado, Jaume Bastida, Joaquim Gascon, Julio Alonso-Padilla
Summary: Chagas disease, caused by Trypanosoma cruzi, is a devastating neglected disease. The discovery of safer and more effective drugs is urgently needed. The AlphaFold Protein Structure Database provides protein models that can help describe new therapeutic approaches and shed light on the molecular mechanisms of known compounds.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Maykon Tavares de Oliveira, Andre Schmidt, Maria Claudia da Silva, Eduardo Antonio Donadi, Joao Santana da Silva, Jose Antonio Marin-Neto
Summary: The study revealed that the blood parasite load in patients with CCC is highly variable and appears to be directly linked to the reduction of LVEF, an important prognostic indicator in CCC patients.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
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
Microbiology
Suzana Marques de Jesus, Leonardo Pinto, Fernanda de Lima Moreira, Glauco Henrique Balthazar Nardotto, Rodrigo Cristofoletti, Luisa Perin, Katia da Silva Fonseca, Pauliana Barbedo, Lorena Cera Bandeira, Paula Melo de Abreu Vieira, Claudia Martins Carneiro
Summary: Chronic infection with Trypanosoma cruzi alters the pharmacokinetics and tissue distribution of benznidazole in mice, potentially impacting the therapeutic dosing regimen. This study suggests that chronic Chagas disease patients may require adjustments in benznidazole pharmacokinetics and dosing due to changes in drug exposure and tissue distribution.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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
Immunology
Kayla J. J. Rayford, Ayorinde Cooley, Anthony W. W. Strode, Inmar Osi, Ashutosh Arun, Maria F. F. Lima, Smita Misra, Siddharth Pratap, Pius N. N. Nde
Summary: Trypanosoma cruzi is the cause of Chagas Disease, which has significant impacts on health and economics globally. This study investigates the dysregulation of a type of small noncoding RNA called piRNAs during early T. cruzi infection, and predicts their interactions with mRNA. The findings suggest that piRNAs play important roles in infection and pathogenesis, and could potentially be used as biomarkers and therapeutic targets for infectious diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Bilal Zulfiqar, Vicky M. Avery
Summary: Despite the development of sophisticated and robust phenotypic in vitro assays in the past decade, there are still limitations and challenges, including variations in activity reported between different research groups and the success of translating in vitro outcomes into in vivo.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Plant Sciences
Darren C. Holland, Dale W. Prebble, Safak Er, Joshua B. Hayton, Luke P. Robertson, Vicky M. Avery, Andrii Domanskyi, Milton J. Kiefel, John N. A. Hooper, Anthony R. Carroll
Summary: Seven new compounds were isolated from an Australian marine organism and further studied. These compounds may have potential for treating protein aggregation issues in neurodegenerative diseases.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Medicinal
Ari S. Nugraha, Yoshinta D. Purnomo, Antonius N. Widhi Pratama, Bawon Triatmoko, Rudi Hendra, Hendris Wongso, Vicky M. Avery, Paul A. Keller
Summary: Malaria is a neglected tropical disease that requires serious efforts to combat. Research into Indonesian medicinal plants Swietenia mahagoni and Pluchea indica identified 5 constituents, with 34,5-tri-O-caffeoylquinic acid (4) showing the highest activity against Plasmodium falciparum 3D7 and Dd2 strains.
NATURAL PRODUCT COMMUNICATIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Lydia Jordaan, Malcolm T. Ndlovu, Sinethemba Mkhize, Siyabonga Ngubane, Leigh Loots, Sandra Duffy, Vicky M. Avery, Prinessa Chellan
Summary: Six cationic half-sandwich Ir(III) and Rh(III) complexes were synthesized and fully characterized. The crystal structures of these complexes were determined by X-ray diffraction. The complexes displayed moderate to good activity against Plasmodium falciparum and were not cytotoxic to human cells.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2022)
Article
Microbiology
Melissa L. Sykes, Emily K. Kennedy, Kevin D. Read, Marcel Kaiser, Vicky M. Avery
Summary: Chagas disease and Human African Trypanosomiasis (HAT) are parasitic diseases that pose a serious threat to human health. The existing treatment methods are not highly effective, thus there is a need for new therapeutic drugs. Through in vitro assays, compounds with selective activity against these parasites have been identified and evaluated for further research and development.
Article
Chemistry, Organic
Kah Yean Lum, Jonathan M. White, Daniel J. G. Johnson, Vicky M. Avery, Rohan A. Davis
Summary: Nine new fluorinated analogues were synthesised using late-stage functionalisation on the Open Source Malaria (OSM) triazolopyrazine scaffold. The structures of all analogues were characterised and their inhibitory activity against Plasmodium falciparum and cytotoxicity against a human embryonic kidney cell line were tested. Some compounds showed moderate antimalarial activity, while none displayed cytotoxicity at high concentrations. Substitution of CF3 and CF2H moieties at the C-8 position significantly reduced antimalarial activity, while incorporation of a CF2Me group completely abolished the effect.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Christoff C. Albertyn, Annick van Niekerk, Sandra Duffy, Vicky M. Avery, Erick Strauss, Prinessa Chellan
Summary: The aim of this study was to improve the activity of artemisinin-based compounds for the treatment of malaria, primarily caused by Plasmodium falciparum. Six new organometallic artemisinin-based complexes were synthesized and characterized, with the ferrocenyl amido-artesunate compound showing the most activity against the chloroquine-resistant strain.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2023)
Article
Plant Sciences
Chen Zhang, Kah Yean Lum, Aya C. Taki, Robin B. Gasser, Joseph J. Byrne, Luis J. Montaner, Ian Tietjen, Vicky M. Avery, Rohan A. Davis
Summary: The study focused on the purification and synthesis of a bioactive compound derived from Eremophila microtheca. A library of carbamate-based compounds was generated using the synthesized compound as a scaffold, and their activities against parasites, malaria, and HIV were evaluated. The results showed promising antiparasitic, antimalarial, and antiviral activities of certain compounds.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Folake A. Egbewande, Brett D. Schwartz, Sandra Duffy, Vicky M. Avery, Rohan A. Davis
Summary: The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, was achieved. Although yields were low, a small library of thiaplakortone A analogues (3-11) was synthesised using a Boc-protected thiaplakortone A (2) as a scaffold for late-stage functionalisation. The antimalarial activity of the new analogues was evaluated, with the mono-brominated analogue (compound 5) showing the best activity against both drug-sensitive and drug-resistant strains of Plasmodium falciparum.
Article
Biology
Louisa C. E. Windus, Nicholas Matigian, Vicky M. M. Avery
Summary: This study aimed to establish a biologically relevant 3D in vitro model that mimics the cellular and molecular profiles of metastasis-associated fibroblasts (MAFs) found in vivo. Using 3D in vitro cell culture models, the bone-derived fibroblast cell line, HS-5, was treated with conditioned media from metastatic-derived prostate cancer cell lines, PC3 and MDA-PCa 2b, or mouse-derived fibroblasts 3T3. The resulting HS5-PC3 and HS5-MDA cell lines displayed alterations in expression levels and genomic profiles consistent with subpopulations of MAFs reported in vivo. The use of these engineered 3D models could provide insights into the novel biology regulating metastatic growth and the role of fibroblasts in the colonization process.
Article
Plant Sciences
Dale W. Prebble, Darren C. Holland, Francesca Ferretti, Joshua B. Hayton, Vicky M. Avery, George D. Mellick, Anthony R. Carroll
Summary: The study suggests a potential link between amyloid protein aggregation and the progression of neurodegenerative conditions and malaria. By screening antiplasmodial active extracts from Australian eucalypt flowers, researchers discovered a compound (Myrtucommulone P) that not only showed affinity to a Parkinson's disease-implicated protein but also exhibited antiplasmodial activity and inhibited protein aggregation. In addition, several other compounds were isolated from E. cloeziana.
JOURNAL OF NATURAL PRODUCTS
(2023)
Editorial Material
Parasitology
Vicky M. Avery
Summary: High-content imaging has provided a powerful tool for understanding the complexities of cell biology, enabling the characterization of specific phenotypes and elucidation of mechanisms of action and resistance in malaria research.
TRENDS IN PARASITOLOGY
(2023)
Article
Chemistry, Medicinal
Chee Wei Ang, Brendon M. Lee, Colin J. Jackson, Yuehong Wang, Scott G. Franzblau, Amanda F. Francisco, John M. Kelly, Paul Bernhardt, Lendl Tan, Nicholas P. West, Melissa L. Sykes, Alexandra O. Hinton, Raghu Bolisetti, Vicky M. Avery, Matthew A. Cooper, Mark A. T. Blaskovich
Summary: Tuberculosis and parasitic infections pose a significant threat to public health and economic growth worldwide. This study explores a new subclass of bicyclic nitroimidazole compounds and their potential as treatments for tuberculosis and Chagas disease, demonstrating promising results in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)