Review
Pharmacology & Pharmacy
Exequiel O. J. Porta, Karunakaran Kalesh, Patrick G. Steel
Summary: Chagas disease, caused by T. cruzi, is a significant public health burden in Latin America, particularly in impoverished regions. There is a lack of effective treatment options, with current medications nifurtimox and benznidazole having serious side effects and low efficacy. Drug repurposing, particularly combination therapy, offers a promising approach to overcome the challenges associated with treating Chagas disease. This review explores recent advances and challenges in drug repurposing, aiming to accelerate the development of new, safe, and effective treatments for Chagas disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Parasitology
Isabela Teresa Santos Correa, Thais Alves da Costa-Silva, Andre Gustavo Tempone
Summary: Manidipine exhibits potent antiparasitic activity against Trypanosoma cruzi, showing potential as a candidate for future investigations in animal models.
Article
Immunology
Cynthia Vanesa Rivero, Santiago Jose Martinez, Paul Novick, Juan Agustin Cueto, Betiana Nebai Salassa, Maria Cristina Vanrell, Xiaomo Li, Carlos Alberto Labriola, Luis Mariano Polo, David M. Engman, Joachim Clos, Patricia Silvia Romano
Summary: T. cruzi, the causal agent of Chagas disease, poses challenges due to its ability to infect different host cells and its resistance to current treatments. Carvedilol, identified through virtual screening, shows promising in vitro and in vivo activity against T. cruzi, making it a potential lead for Chagas disease treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
W. M. Valsecchi, J. M. Delfino, J. Santos, S. H. Fernandez Villamil
Summary: The study found that bisphosphonates can significantly inhibit the growth of T. cruzi, with a strong correlation to the inhibition of TcHPRT activity, suggesting TcHPRT as a crucial target for drug development. Additionally, zoledronate was shown to interfere with the cell infection process of the parasite, providing a new direction for antiparasitic drug development.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Microbiology
A. J. Berenstein, N. Falk, G. Moscatelli, S. Moroni, N. Gonzalez, F. Garcia-Bournissen, G. Ballering, H. Freilij, J. Altcheh
Summary: The study found that adverse drug reactions (ADRs) associated with Nifurtimox treatment for Chagas disease were relatively rare and mainly mild to moderate. ADRs primarily affected the nutritional, central nervous, and digestive systems, with no significant differences between adults and children. The proportion of treatment discontinuations due to ADRs was higher in adults compared to children.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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
Microbiology
Ramendra P. Pandey, Marilda Savoia Nascimento, Caio Haddad Franco, Karina Bortoluci, Marcelo Nunes Silva, Bianca Zingales, Daniel Gibaldi, Leda Castano Barrios, Joseli Lannes-Vieira, Leonardo Moro Cariste, Jose Ronnie Vasconcelos, Carolina Borsoi Moraes, Lucio H. Freitas-Junior, Jorge Kalil, Laura Alcantara, Edecio Cunha-Neto
Summary: The study investigated the effects of repurposed drugs chloroquine and colchicine on the treatment of Chagas disease, and found that the combination of chloroquine and benznidazole could enhance the trypanocidal activity of benznidazole, reducing the required dosage. In vivo experiments in mice also showed the effectiveness of the combination therapy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Lucio Rivera-Santiago, Ignacio Martinez, Ruben Arroyo-Olarte, Paulina Diaz-Garrido, Roberto I. Cuevas-Hernandez, Bertha Espinoza
Summary: This study aimed to describe the structural characteristics of TcMPX and compare it with other PRXs, as well as reposition the antibiotic Thiostrepton as a potential inhibitor molecule. The results showed a high structural similarity between TcMPX and human PRX3, and demonstrated that Thiostrepton could affect the function of TcMPX and reduce the proliferation of T. cruzi.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Oncology
Mark P. Lythgoe, Vinay Prasad
Summary: Canakinumab, an anti-interleukin-1 beta monoclonal antibody, has been approved for the treatment of immune-related disorders. It has shown potential in reducing the occurrence and mortality of lung cancer, leading to further clinical trials. However, the initial trials targeting cancer have not met their primary efficacy endpoints.
BRITISH JOURNAL OF CANCER
(2022)
Article
Chemistry, Medicinal
Minerva Arce-Fonseca, Rodolfo Andres Gutierrez-Ocejo, Jose Luis Rosales-Encina, Alberto Aranda-Fraustro, Juan Jose Cabrera-Mata, Olivia Rodriguez-Morales
Summary: This study aimed to evaluate the efficacy of nitazoxanide against the Mexican T. cruzi Ninoa strain in mice. The results showed that nitazoxanide can reduce parasitemia, indirectly induce IgG antibody production, and partially prevent histopathological damage.
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
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.
Review
Oncology
Fangting You, Caiyi Zhang, Xiaoxiao Liu, Daofei Ji, Tong Zhang, Rutong Yu, Shangfeng Gao
Summary: Psychotropic drugs, in addition to their use in mental disorders, have potential for cancer therapy, particularly for glioma. They can inhibit malignant progression of glioma by targeting signaling pathways or increasing sensitivity of glioma cells to conventional treatments. Repurposing established psychotropic drugs as anticancer agents provides new options for glioma treatment.
Review
Biochemistry & Molecular Biology
Izabela Rumienczyk, Maria Kulecka, Malgorzata Statkiewicz, Jerzy Ostrowski, Michal Mikula
Summary: Despite no approved treatment for sepsis, preclinical studies have shown the potential of oncology drugs in improving sepsis. Further testing of standard and oncology drug combinations holds promise for better clinical outcomes in sepsis.
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
Plant Sciences
Vitor F. Freire, Juliana R. Gubiani, Tara M. Spencer, Eduardo Hajdu, Antonio G. Ferreira, Dayana A. S. Ferreira, Erica de Castro Levatti, Joanna E. Burdette, Carlos Henrique Camargo, Andre G. Tempone, Roberto G. S. Berlinck
Summary: This study investigated the marine sponge Agelas dispar and discovered new bromopyrrole-derived metabolites using feature-based molecular networking, dereplication, and isolation techniques. The compounds were identified by analyzing spectroscopic data and MS/MS fragmentation. The antimicrobial activity of the isolated compounds was evaluated, and dibromoageliferin showed the strongest activity against multi-drug-resistant pathogenic bacteria.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Pharmacology & Pharmacy
Cleber C. Melo-Filho, Tesia Bobrowski, Holli-Joi Martin, Zoe Sessions, Konstantin I. Popov, Nathaniel J. Moorman, Ralph S. Baric, Eugene N. Muratov, Alexander Tropsha
Summary: This study identified highly conserved binding sites in key coronavirus proteins, providing important information for the development of broad-spectrum anti-coronaviral medications, and validated the significance of this conservation for drug discovery with existing experimental data.
ANTIVIRAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Maiara M. Romanelli, Maiara Amaral, Fernanda Thevenard, Lucas M. Santa Cruz, Luis O. Regasini, Alvaro E. Migotto, Joao Henrique G. Lago, Andre G. Tempone
Summary: In this study, a new compound BMA was isolated and characterized from a marine coral. It was found that BMA exhibited inhibitory effects against T. cruzi without cytotoxicity to mammalian cells. The mechanism of action of BMA involved the depolarization of mitochondrial membrane potential and reduction of intracellular calcium levels, leading to decreased ATP levels and growth inhibition of T. cruzi.
Article
Biochemistry & Molecular Biology
Erica V. de Castro Levatti, Thais A. Costa-Silva, Thiago R. Morais, Joao Paulo S. Fernandes, Joao Henrique G. Lago, Andre G. Tempone
Summary: Natural metabolites have a diverse range of chemical structures and have inspired the development of new drugs. In this study, three semi-synthetic derivatives of natural neolignane licarin A were prepared and evaluated for their activity against Leishmania (L.) infantum. Compound 1b showed activity against the parasites without inducing hemolytic or cytotoxic effects on mammalian cells. Compound 1c exhibited promising selectivity and induced lethal alterations in the bioenergetic and protein metabolism of Leishmania.
Article
Parasitology
Luca S. F. Nesic de Freitas, Cristiane Franca da Silva, Sebastiano Intagliata, Emanuele Amata, Loredana Salerno, Maria de Nazare Correia Soeiro
Summary: Aspirin and its derivatives have been found to be effective in treating malignant tumors, exhibiting strong inhibitory effects on their proliferation and metastasis. These drugs have good bioavailability and acceptable bio-toxicity properties, suggesting they may be a new, safer, and more effective therapy for CD.
Article
Chemistry, Medicinal
Paulo Ricardo Pimenta da Silva Ramos, Melina Mottin, Caroline Sprengel Lima, Leticia R. Assis, Ketllyn Zagato de Oliveira, Nathalya Cristina de Moraes Roso Mesquita, Natasha Marques Cassani, Igor Andrade Santos, Joyce Villa Verde Bastos Borba, Vinicius Alexandre Fiaia Costa, Bruno Junior Neves, Rafael Victorio Carvalho Guido, Glaucius Oliva, Ana Carolina Gomes Jardim, Luis Octavio Regasini, Carolina Horta Andrade
Summary: This study used computational approaches to screen for compounds that can inhibit ZIKV and identified pedalitin and quercetin as potential anti-ZIKV drug candidates.
Article
Biology
Maiara Amaral, Marina T. Varela, Ravi Kant, Myron Christodoulides, Joao Paulo S. Fernandes, Andre G. Tempone
Summary: Chagas disease, caused by Trypanosoma cruzi, affects 7 million people worldwide, especially in developing countries, and current treatments have limited efficacy. The natural alkylphenol, gibbilimbol B, and its synthetic derivatives, LINS03018 (1) and LINS03024 (2), showed promising antiparasitic activity. Mechanism studies revealed that compound 1 affects bioenergetics metabolism and impairs mitochondria, while compound 2 only affects mitochondrial membrane potential. This work highlights the importance of investigating the mechanism of action during early stages of drug discovery.
Article
Biochemistry & Molecular Biology
Milene Aparecida Andrade, Melina Mottin, Bruna K. de P. Sousa, Joao Alexandre Ribeiro Goncalves Barbosa, Clenia dos Santos Azevedo, Camila Lasse Silva, Marina Goncalves de Andrade, Flavia Nader Motta, Christine Maulay-Bailly, Severine Amand, Jaime Martins de Santana, Carolina Horta Andrade, Philippe Grellier, Izabela M. D. Bastos
Summary: This study screened 2,320 compounds from the chemical library of the Museum National d'Histoire Naturelle of Paris, and identified five compounds with high inhibitory activity against ZIKV NS2B-NS3 protease, including 2-(3-methoxyphenoxy) benzoic acid.
Article
Chemistry, Medicinal
Amanda Alves de Oliveira, Livia do Carmo Silva, Bruno Junior Neves, Vinicius Alexandre Fiaia Costa, Eugene N. Muratov, Carolina Horta Andrade, Celia Maria de Almeida Soares, Vinicius M. Alves, Maristela Pereira
Summary: This study aims to discover new anti-Paracoccidioides compounds through computational strategies. The researchers collected and curated a library of compounds tested against Paracoccidioides spp., conducted experimental evaluations, and used computational tools to identify potential targets for the most active compounds. Seven compounds showed activity against Paracoccidioides spp., making them potential candidates for developing new compounds.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jade Milhomem Lemos, Meryck Felipe Brito da Silva, Alexandra Maria dos Santos Carvalho, Henric Pietro Vicente Gil, Vinicius Alexandre Fiaia Costa, Carolina Horta Andrade, Rodolpho Campos Braga, Philippe Grellier, Eugene N. Muratov, Sebastien Charneau, Jose Teofilo Moreira-Filho, Izabela Marques Dourado Bastos, Bruno Junior Neves
Summary: This study created an explainable multitask pipeline to profile the activity of compounds against three trypanosomes, successfully discovering four new experimental hits, among which LC-6 showed promising results. The results demonstrate that the multitask protocol offers predictivity and interpretability in virtual screening, potentially improving hit rates in Chagas and human African trypanosomiasis projects.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
A. B. C. Marcos Junior, Livia C. Silva, Olivia B. Rocha, Amanda A. Oliveira, Igor G. Portis, Antonio Alonso, Lais Alonso, Kleber S. F. Silva, Marcelo N. Gomes, Carolina H. Andrade, Celia M. A. Soares, Maristela Pereira
Summary: A proteomic approach was used to investigate the metabolic changes caused by a chalcone derivative (LabMol-75) in Paracoccidioides brasiliensis yeast cells. The compound downregulated proteins associated with glycolysis, & beta;-oxidation, the citrate cycle, and the electron transport chain, resulting in an energetic imbalance and oxidative stress.
FUTURE MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Amanda de Oliveira Matos, Pedro Henrique dos Santos Dantas, Mike Telemaco Contreras Colmenares, Geraldo Rodrigues Sartori, Marcelle Silva-Sales, Joao Herminio Martins Da Silva, Bruno Junior Neves, Carolina Horta Andrade, Helioswilton Sales-Campos
Summary: Researchers used computational simulations to investigate the potential binding domains between TREM-1 and its five known ligands. They found that the complementarity-determining regions, especially the CDR3 loop, were the main mediators of antigen recognition. This study provides a structural basis for understanding the recognition process of TREM-1 and may be valuable for future computational and biological investigations.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Maiara Amaral, Hannah Asiki, Claire E. Sear, Snigdha Singh, Pauline Pieper, Marius M. Haugland, Edward A. Anderson, Andre G. Tempone
Summary: Visceral leishmaniasis is a deadly neglected protozoan disease. There is a need for new drugs due to the limitations of existing treatments. This study explored the potential of synthetic compounds based on dehydrodieugenol B for the treatment of the disease, identifying compound 24 as the most promising with high potency and low toxicity.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jose Teofilo Moreira-Filho, Bruno Junior Neves, Rayssa Araujo Cajas, Josue de Moraes, Carolina Horta Andrade
Summary: Machine learning models were used to predict the schistosomicidal activity of untested compounds. Four compounds demonstrated significant activity against schistosomula without toxicity in animal and human cell lines.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Joshua E. Hochuli, Sankalp Jain, Cleber Melo-Filho, Zoe L. Sessions, Tesia Bobrowski, Jun Choe, Johnny Zheng, Richard Eastman, Daniel C. Talley, Ganesha Rai, Anton Simeonov, Alexander Tropsha, Eugene N. Muratov, Bolormaa Baljinnyam, Alexey Zakharov
Summary: This study investigates whether compounds that bind the human angiotensin-converting enzyme 2 (ACE2) protein can reduce SARS-CoV-2 replication without affecting ACE2's enzymatic function. Through screening and in silico techniques, 73 ACE2 binders were identified, and five of them were found to inhibit the viral life cycle in human cells. These compounds serve as valuable starting points for the development of acute treatments for COVID-19 and research into host-directed therapy.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)