BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis and antitrypanosomatid activity of 2-nitroimidazole-3,5-disubstituted isoxazole compounds based on benznidazole. 2023

Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Laboratório de Síntese e Química Medicinal (LASQUIM), Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grossso do Sul- UFMS, Campo Grande, Mato Grosso do Sul, CEP 79051-470, Brazil.

Chagas disease and leishmaniasis are neglected diseases of high priority as a public health problem. Pharmacotherapy is based on the administration of a few drugs, which exhibit hazardous adverse effects and toxicity to the patients. Thus, the search for new antitrypanosomatid drugs is imperative to overcome the limitations of the treatments. In this work, 46 2-nitroimidazole 3,5-disubstituted isoxazole compounds were synthesized in good yields by [3 + 2] cycloaddition reaction between terminal acetylene (propargyl-2-nitroimidazole) and chloro-oximes. The compounds were non-toxic to LLC-MK2 cells. Compounds 30, 35, and 44 showed in vitro antichagasic activity, 15-fold, 12-fold, and 10-fold, respectively, more active than benznidazole (BZN). Compounds 30, 35, 44, 45, 53, and 61 acted as substrates for the TcNTR enzyme, indicating that this might be one of the mechanisms of action involved in their antiparasitic activity. Piperazine series and 4-monosubstituted compounds were potent against T. cruzi parasites. Besides the in vitro activity observed in compound 45, the in vivo assay showed that the compound only reduced the parasitemia levels by the seventh-day post-infection (77%, p > 0.001) compared to the control group. However, 45 significantly reduced the parasite load in cardiac tissue (p < 0.01) 11 days post-infection. Compounds 49, 52, and 54 showed antileishmanial activity against intracellular amastigotes of Leishmania (L.) amazonensis at the same range as amphotericin B. These findings highlight the antitrypanosomatid properties of 2-nitroimidazole 3,5-disubstituted isoxazole compounds and the possibility in using them as antitrypanosomatid agents in further studies.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D009593 Nitroimidazoles IMIDAZOLES having a nitro moiety. Nitroimidazole
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000981 Antiprotozoal Agents Substances that are destructive to protozoans. Schizonticides,Agents, Antiprotozoal
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014349 Trypanosoma cruzi The agent of South American trypanosomiasis or CHAGAS DISEASE. Its vertebrate hosts are man and various domestic and wild animals. Insects of several species are vectors. Trypanosoma cruzus,cruzi, Trypanosoma
D014355 Chagas Disease Infection with the protozoan parasite TRYPANOSOMA CRUZI, a form of TRYPANOSOMIASIS endemic in Central and South America. It is named after the Brazilian physician Carlos Chagas, who discovered the parasite. Infection by the parasite (positive serologic result only) is distinguished from the clinical manifestations that develop years later, such as destruction of PARASYMPATHETIC GANGLIA; CHAGAS CARDIOMYOPATHY; and dysfunction of the ESOPHAGUS or COLON. Trypanosomiasis, South American,American Trypanosomiasis,Chagas' Disease,Trypanosoma cruzi Infection,Infection, Trypanosoma cruzi,Infections, Trypanosoma cruzi,South American Trypanosomiasis,Trypanosoma cruzi Infections,Trypanosomiasis, American
D061565 Cycloaddition Reaction Synthetic organic reactions that use reactions between unsaturated molecules to form cyclical products. Cycloaddition,Cycloaddition Reaction Techniques,Diels-Alder Reaction,Cycloaddition Reaction Technique,Cycloaddition Reactions,Diels Alder Reaction,Reaction Technique, Cycloaddition,Reaction Techniques, Cycloaddition,Reaction, Cycloaddition,Reaction, Diels-Alder,Reactions, Cycloaddition,Technique, Cycloaddition Reaction,Techniques, Cycloaddition Reaction

Related Publications

Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G.
March 2019, Chemical biology & drug design,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5-disubstituted isoxazole compounds based on 5-nitrofuran scaffolds.
February 2020, Archiv der Pharmazie,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study.
November 2020, ChemMedChem,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates.
September 2021, Bioorganic chemistry,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
3,5-Disubstituted Isoxazole Derivatives: Potential Inhibitors of Inflammation and Cancer.
February 2016, Inflammation,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Design, Synthesis, and Antiproliferative Activity of Benzopyran-4-One-Isoxazole Hybrid Compounds.
May 2023, Molecules (Basel, Switzerland),
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Design, synthesis and pro-apoptotic antitumour properties of indole-based 3,5-disubstituted oxadiazoles.
October 2010, European journal of medicinal chemistry,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Versatile synthesis of 3,5-disubstituted 2-fluoropyridines and 2-pyridones.
April 2003, The Journal of organic chemistry,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
Synthesis and antimycobacterial activity of 3,5-disubstituted thiadiazine thiones.
October 2003, Bioorganic & medicinal chemistry,
Diego B Carvalho, and Pedro A N Costa, and Gisele B Portapilla, and Amarith R das Neves, and Cristiane Y K Shiguemoto, and Bruno I Pelizaro, and Fernanda Silva, and Eliane M Piranda, and Carla C P Arruda, and Priscyla D M Gaspari, and Iara A Cardoso, and Pedro H Luccas, and M Cristina Nonato, and Norberto P Lopes, and Sergio de Albuquerque, and Adriano C M Baroni
3,5-Disubstituted Thiazolidine-2,4-Diones: Design, Microwave-Assisted Synthesis, Antifungal Activity, and ADMET Screening.
September 2018, SLAS discovery : advancing life sciences R & D,
Copied contents to your clipboard!