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
Jakob Bouton, Ludmila Ferreira de Almeida Fiuza, Camila Cardoso Santos, Maria Angela Mazzarella, Maria de Nazare Correia Soeiro, Louis Maes, Izet Karalic, Guy Caljon, Serge Van Calenbergh
Summary: Chagas disease and visceral leishmaniasis are neglected tropical diseases with insufficient current treatments, requiring the development of new drugs. This study reports the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides as potential antiparasitic agents, with one compound showing activity in an acute Chagas disease mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Vinay Shankar Tiwari, Prince Joshi, Kanchan Yadav, Anamika Sharma, Sushobhan Chowdhury, Ashan Manhas, Niti Kumar, Renu Tripathi, Wahajul Haq
Summary: A series of novel 4-aminoquinoline analogues with a methyl group were synthesized and evaluated for their antimalarial activity, showing good potential in inhibiting Plasmodium falciparum with low toxicity levels. The introduction of a 4-methylamino substitution is well tolerated and holds promise for the discovery of new antimalarial agents against drug-resistant malaria.
Article
Immunology
Berta Barnadas-Carceller, Nieves Martinez-Peinado, Laura Cordoba Gomez, Albert Ros-Lucas, Juan Carlos Gabaldon-Figueira, Juan J. Diaz-Mochon, Joaquim Gascon, Ignacio J. Molina, Maria Jose Pineda de las Infantas y Villatoro, Julio Alonso-Padilla
Summary: Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease with significant impact in the Americas. The efficacy of available drugs in the chronic stage of the disease is reduced, requiring the development of safer and more effective alternatives. Targeting the purine salvage pathway, which the parasite relies on for acquiring purines, has shown promise as a strategy for new drug development.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Parasitology
Natali de Franca Nibbering Santos, Natanael da Silva Bezerra Jr, Jamerson Ferreira de Oliveira, Denise Maria Figueiredo Araujo Duarte, Jose Cleberson dos Santos Soares, Diego Santa Clara Marques, Aline Caroline da Silva Santos, Fatima Nogueira, Valeria Rego Alves Pereira, Maria Carmo Alves de Lima, Iranildo Jose da Cruz Filho
Summary: In this study, 13 thiosemicarbazones and 16 thiazoles were synthesized and characterized. The pharmacokinetic properties of these compounds showed good bioavailability and permeability. Thiosemicarbazones exhibited moderate to high antioxidant potential and could interact with albumin and DNA. They also showed lower toxicity to mammalian cells compared to thiazoles. Both thiosemicarbazones and thiazoles exhibited cytotoxic potential against Leishmania amazonensis and Trypanosoma cruzi parasites. However, thiosemicarbazones did not inhibit the growth of Plasmodium falciparum, while thiazoles showed growth inhibition. This study suggests that the synthesized compounds have in vitro antiparasitic potential.
EXPERIMENTAL PARASITOLOGY
(2023)
Article
Multidisciplinary Sciences
Eva Dolezelova, Tomas Klejch, Petr Spacek, Martina Slapnickova, Luke Guddat, Dana Hockova, Alena Zikova
Summary: Medically important unicellular protozoans rely on the purine salvage pathway (PSP) as they cannot synthesize purines de novo. A Trypanosoma brucei enzyme involved in the salvage of adenine, adenine phosphoribosyl transferase (APRT), was characterized, and potential inhibitors were designed. These inhibitors showed anti-trypanosomal activity, suggesting they can be further explored for their actual target(s) in T. brucei.
SCIENTIFIC REPORTS
(2021)
Review
Chemistry, Medicinal
Eyra Ortiz-Perez, Gildardo Rivera, Cristian O. Salas, Juan J. Zarate-Ramos, Oleksandra S. Trofymchuk, Lucio Hernandez-Soberanis, Juanita D. Perales-Flores, Karina Vazquez
Summary: Naphthoquinones are aromatic compounds with antibacterial, antifungal, and antiprotozoal properties, which can be obtained from both natural and synthetic sources. Research on naphthoquinones and their derivatives contributes to the development of new chemotherapeutic agents against parasitic diseases.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Danielle Figueredo da Silva, Jessica Lima de Souza, Diego Mota da Costa Jr, David Bacelar Costa, Paulo Otavio Lourenco Moreira, Amanda Luisa da Fonseca, Fernando de Pilla Varotti, Jorddy Neves Cruz, Cleydson Breno Rodrigues dos Santos, Clayton Queiroz Alves, Franco Henrique Andrade Leite, Hugo Neves Brandao
Summary: This study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum. The results showed that auraptene and poligalen exhibited antiplasmodial activity against Plasmodium falciparum, with high selectivity indexes. Molecular dynamics studies demonstrated the stability of coumarins at the binding site and favorable binding energies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Bemba Sidi Mohamed, Minh Chau Nguyen, Sharon Wein, Jean-Pierre Uttaro, Xavier Robert, Sebastien Violot, Lionel Ballut, Vinesh Jugnarain, Christophe Mathe, Rachel Cerdan, Nushin Aghajari, Suzanne Peyrottes
Summary: The nucleotidase ISN1 is a potential therapeutic target of the purine salvage pathway of Plasmodium falciparum. PfISN1 ligands were identified through in silico screening and thermal shift assays. The most potent inhibition of the parasite in vitro was achieved by purine derivatives such as compounds 1, (±)-7e, and β-L-(thorn)-2, which have low micromolar IC50 values.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Theresa Hermann, Robin Wallner, Johanna Dolensky, Werner Seebacher, Eva-Maria Pferschy-Wenzig, Marcel Kaiser, Pascal Maser, Robert Weis
Summary: The compound MMV030666 in MMV's Malaria Box exhibits multi-stage activity against various strains of Plasmodium falciparum without resistance development. By modifying the structure, a series of compounds were prepared and the relationship between the structure and activity was revealed. Furthermore, the pharmacokinetic and physicochemical parameters were improved.
Article
Biochemistry & Molecular Biology
Leonardo S. Lara, Guilherme C. Lechuga, Caroline dos S. Moreira, Thais B. Santos, Vitor F. Ferreira, David R. da Rocha, Mirian C. S. Pereira
Summary: Chagas disease remains a serious public health problem in Latin America, with current clinical treatments considered inadequate, emphasizing the need for discovering new effective and safe drugs. Research analyzed a series of naphthoquinone derivatives for biological activity and structure-activity relationship, identifying 1g as a promising compound against Trypanosoma cruzi. However, current compounds were unable to reduce parasite load or prevent mouse mortality in infection.
Article
Multidisciplinary Sciences
Nerea Escala, Laura M. Pineda, Michelle G. Ng, Lorena M. Coronado, Carmenza Spadafora, Esther del Olmo
Summary: Malaria cases and deaths remain high, mainly due to increased resistance to antimalarials. The search for new molecules to replace current drugs is essential. This study presents the synthesis of benzimidazole derivatives and evaluates their activity against P. falciparum HB3 strain. Compounds with electron donating groups on ring A and pyridine type structure on ring B show favorable activity. Two molecules display high nanomolar range antiplasmodial activity and selectivity indexes above 10. They seem to use a different pathway than chloroquine and most antimalarials.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Rong-Zhen Wu, Huai-Yu Zhou, Jing-Feng Song, Qiao-Hong Xia, Wei Hu, Xiao-Dong Mou, Xun Li
Summary: This paper summarizes the current research status and prospects for more effective and safer chemotherapeutic drugs for chronic latent toxoplasmosis infection caused by the Toxoplasma parasite. The emphasis is on possible molecular biotargets and the binding modes and structure-activity relationship profiles of corresponding inhibitors. The information provided in this paper is expected to help in the further identification of more effective chemotherapeutic interventions for preventing and treating zoonotic infections caused by Toxoplasma gondii.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Marie Miglianico, Judith M. Bolscher, Martijn W. Vos, Karin J. M. Koolen, Marloes de Bruijni, Deeya S. Rajagopal, Emily Chen, Michael Kiczun, David Gray, Brice Campo, Robert W. Sauerwein, Koen J. Dechering
Summary: This study reveals that chemical intervention against malaria parasites mostly occurs during the liver schizogony stage, with limited effects on sporozoite viability and motility. However, ten compounds showed significant impact on liver schizont development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ludmila F. de A. Fiuza, Denise G. J. Batista, Roberson D. Girao, Fabian Hulpia, Paula Finamore-Araujo, Mustafa M. Aldfer, Ehab Kotb Elmahallawy, Harry P. De Koning, Otacilio Moreira, Serge Van Calenbergh, Maria de Nazare C. Soeiro
Summary: Chagas disease, caused by Trypanosoma cruzi, is a serious public health problem without effective and safe treatment options. Nucleoside analogues, due to their different substrate specificities, show promise as a therapeutic alternative for Chagas disease. In this study, certain tubercidin derivatives were found to be highly potent and selective against T. cruzi, with their uptake mediated by the nucleoside transporter TcrNT2. These compounds effectively reduced parasitemia in cardiac cultures and showed no noticeable toxicity in mice. Further studies and combination evaluations are needed to identify more effective and safer therapies for Chagas disease.
Article
Immunology
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Jimy Pinto, Gimena Rojas, Alejandro Palacios, Fabiana Barreira, Bethania Blum, Alejandro Gabriel Schijman, Michel Vaillant, Nathalie Strub-Wourgaft, Maria Jesus Pinazo, Graeme Bilbe, Isabela Ribeiro
Summary: The study found that fexinidazole may be a potential drug for the treatment of chronic indeterminate Chagas disease. In the 12-month follow-up after treatment, all treated patients with available data showed clearance of parasites, while no patients in the placebo group achieved this effect. Further analysis suggested that low dosages of fexinidazole may be safe and effective.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Biophysics
Agustin Robles-Remacho, M. Angelica Luque-Gonzalez, F. Javier Lopez-Delgado, Juan J. Guardia-Monteagudo, Mario Antonio Fara, Salvatore Pernagallo, Rosario M. Sanchez-Martin, Juan Jose Diaz-Mochon
Summary: The detection of genomic variations in repetitive sequences is crucial for understanding their biological implications. However, there is a lack of techniques to validate the sequencing data obtained from repetitive sequences, especially in the case of single-nucleotide variations (SNVs). This study presents chemFISH, an innovative method for detecting SNVs in repetitive sequences, using dynamic chemistry labelling and abasic peptide nucleic acid probes. ChemFISH allows for rapid and accurate detection of alpha-satellite DNA with single-base resolution. The method demonstrates high sensitivity and specificity, making it a potential tool for validating and discovering SNVs in repetitive sequences.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Immunology
Berta Barnadas-Carceller, Nieves Martinez-Peinado, Laura Cordoba Gomez, Albert Ros-Lucas, Juan Carlos Gabaldon-Figueira, Juan J. Diaz-Mochon, Joaquim Gascon, Ignacio J. Molina, Maria Jose Pineda de las Infantas y Villatoro, Julio Alonso-Padilla
Summary: Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease with significant impact in the Americas. The efficacy of available drugs in the chronic stage of the disease is reduced, requiring the development of safer and more effective alternatives. Targeting the purine salvage pathway, which the parasite relies on for acquiring purines, has shown promise as a strategy for new drug development.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Mary Cruz Torrico, Anna Fernandez-Arevalo, Cristina Ballart, Marco Solano, Ernesto Rojas, Alba Abras, Fabiola Gonzales, Albert Arnau, Silvia Tebar, Teresa Llovet, Daniel Lozano, Eva Ariza-Vioque, Joaquim Gascon, Albert Picado, Faustino Torrico, Carmen Munoz, Montserrat Gallego
Summary: The objective of the study was to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species in Bolivia. All of the isolates could be identified, and no misidentifications were observed at the complex level. MALDI-TOF MS can be used as an alternative to molecular techniques for the identification of Leishmania spp., and its simplicity and cost-effectiveness make it a valuable tool in improving patient management and control of tegumentary leishmaniasis in Bolivia.
MICROBIOLOGY SPECTRUM
(2023)
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
Biophysics
Carmen Martin-Sierra, Mavys Tabraue Chavez, Pablo Escobedo, Victor Garcia-Cabrera, Francisco Javier Lopez-Delgado, Juan Jose Guardia-Monteagudo, Isidoro Ruiz-Garcia, Miguel M. Erenas, Rosario Maria Sanchez-Martin, Luis Fermin Capitan-Vallvey, Alberto J. Palma, Salvatore Pernagallo, Juan Jose Diaz-Mochon
Summary: The COVID-19 pandemic has emphasized the need for innovative diagnostic approaches. CoVradar, a novel colorimetric method, combines nucleic acid analysis, dynamic chemical labeling (DCL) technology, and the Spin-Tube device for detecting SARS-CoV-2 RNA in saliva samples. This method includes a fragmentation step using abasic peptide nucleic acid probes and biotinylated SMART bases for labeling and analysis. Signals are generated through recognition and incubation with a chromogenic substrate, and results are interpreted using CoVreader, a smartphone-based image processing system. CoVradar and CoVreader offer a molecular assay for SARS-CoV-2 RNA detection without the need for extraction or pre-labeling, providing advantages in time, cost, and simplicity.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Pharmacology & Pharmacy
Alejandro Cueto-Sanchez, Hao Niu, Ismael Alvarez-Alvarez, Barbara Lopez-Longarela, Enrique Del Campo-Herrera, Aida Ortega-Alonso, Miren Garcia-Cortes, Jose Pinazo-Bandera, Judith Sanabria-Cabrera, Juan Jose Diaz-Mochon, M. Isabel Lucena, Raul J. Andrade, Camilla Stephens, Mercedes Robles-Diaz
Summary: Detection and characterization of idiosyncratic drug-induced liver injury (DILI) is currently limited by suboptimal standard liver tests. This study evaluated the potential of osteopontin, cytokeratin-18 (ccK18 and K18), α-glutathione-S-transferase and microRNA-122 as new DILI biomarkers.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
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
Multidisciplinary Sciences
Vanessa Smer-Barreto, Andrea Quintanilla, Richard J. R. Elliott, John C. Dawson, Jiugeng Sun, Victor M. Campa, Alvaro Lorente-Macias, Asier Unciti-Broceta, Neil O. Carragher, Juan Carlos Acosta, Diego A. Oyarzun
Summary: Cellular senescence is a stress response involved in aging and various diseases, and the discovery of new senolytics is limited. In this study, the authors used machine learning models trained on published data to identify three senolytic compounds, resulting in significant cost reduction in drug screening. These compounds have comparable potency to known senolytics, and one of them, oleandrin, shows improved potency compared to existing alternatives. This approach demonstrates the potential of artificial intelligence in utilizing heterogeneous drug screening data for early-stage drug discovery.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Antonio Marin-Romero, Valerie Regele, Dajana Kolanovic, Manuela Hofner, Juan Jose Diaz-Mochon, Christa Noehammer, Salvatore Pernagallo
Summary: This study compared the performance of two Luminex platforms, MAGPIX and FLEXMAP 3D, in detecting miR-122-5p using the DCL method. Both platforms showed high sensitivity and specificity in detecting miR-122-5p in serum samples from patients with liver injury. FLEXMAP 3D had a lower limit of detection and slightly better performance compared to MAGPIX.
Article
Chemistry, Analytical
Antonio Marin-Romero, Valerie Regele, Dajana Kolanovic, Manuela Hofner, Juan Jose Diaz-Mochon, Christa Noehammer, Salvatore Pernagallo
Summary: This study compared the performance of two Luminex platforms, MAGPIX and FLEXMAP 3D, in detecting miR-122-5p in serum samples from patients with liver injury. Both platforms showed high sensitivity and specificity, with FLEXMAP 3D exhibiting a lower limit of detection. The precision of miR-122-5p detection was similar between the two platforms. In conclusion, both MAGPIX and FLEXMAP 3D, in conjunction with DCL reagents, proved to be reliable and sensitive tools for detecting miR-122-5p in serum samples from patients with liver injury, with FLEXMAP 3D showing slightly better performance.
Article
Biochemistry & Molecular Biology
Daniel J. Baillache, Teresa Valero, Alvaro Lorente-Macias, David Jonathan Bennett, Richard J. R. Elliott, Neil O. Carragher, Asier Unciti-Broceta
Summary: This study explored antiproliferative compounds for GBM treatment and established structure-antiproliferative activity relationships through the synthesis and screening of small compound libraries. Through a series of design, synthesis, and screening, potent CSF-1R inhibitors with significant antiproliferative activity were discovered.
RSC MEDICINAL CHEMISTRY
(2023)