Research Grants 16/25112-4 - Peptídeo hidrolases, Cisteína proteases - BV FAPESP
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Evaluation of modulators of the activity of proteases involved in pathological processes

Abstract

Proteases are involved in many physiological processes attending to the metabolic and functional demand of the organisms to which they participate. However, in many situations these same proteases can trigger unwanted processes that establish pathologies in humans. Therefore, the modulation of its activities is a way of controlling its actions in pathogenic mechanisms such as tumor progression, metastasis, viral capsid processing, bacterial toxin processing, in facilitating the invasion of parasitic microorganisms and fungi. Among these proteases we have the cysteine proteases lysosomal cathepsins L and B. Cathepsins, in addition to their role in metastatic processes, are also responsible for an important role in the execution of the apoptotic program in several types of tumoral strains, since this enzyme needs to be transferred from the lysosome to the cytosol, where it degrades proteins involved in apoptosis. Cathepsins are involved in programmed cell death and senescence, and in the control of cell proliferation and differentiation. By their deleterious actions in the human organism, these proteases become interesting targets for the development of new drugs. In this context, our objective is to evaluate two families of molecules, one belonging to the alkyltriazoles and alkylphospholipids (21 molecules) and another belonging to the organometallic palladium complexes (8 molecules). In order to do so, we will carry out a screening of inhibitory activity, determination of inhibitory potential IC50, determination of inhibition mechanism and constant of dissociation of inhibitor Ki, determination of the microscopic constants belonging to Ki = k -3 / k3 by time course kinetics, molecular docking having the kinetic data as beacon parameters for modeling. We will evaluate the cytotoxicity of the compounds on leukemic cell lines using flow cytometry and determining the type of cell death. (AU)

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Scientific publications (19)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COELHO, CAMILA M.; DOS SANTOS, THIAGO; FREITAS, POLIANY G.; NUNES, JULIANA B.; MARQUES, MARCOS J.; PADOVANI, CAMILA G. D.; JUDICE, WAGNER A. S.; CAMPS, IHOSVANY; DA SILVEIRA, NELSON J. F.; CARVALHO, DIOGO T.; et al. Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Eugenol Esters as Leishmanicidal Agents. Journal of the Brazilian Chemical Society, v. 29, n. 4, p. 715-728, . (16/25112-4)
DE NOVAIS, LEICE M. R.; DE ARUEIRA, CAUANE C. O.; FERREIRA, LUIZ F.; RIBEIRO, TEREZA A. N.; SOUSA, JR., PAULO T.; JACINTO, MARCOS J.; DE CARVALHO, MARIO G.; JUDICE, WAGNER A. S.; JESUS, LARISSA O. P.; DE SOUZA, ALINE A.; et al. 4 `-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L. Fitoterapia, v. 132, p. 26-29, . (16/25112-4)
PAPP, LUIZ ANTONIO; RODRIGUES, FLAVIO APARECIDO; DE SOUZA JUDICE, WAGNER ALVES; ARAUJO, WELINGTON LUIZ. Onsite Wastewater Treatment Upgrade for Water Reuse in Cooling Towers and Toilets. WATER, v. 14, n. 10, p. 14-pg., . (17/12510-4, 21/01503-2, 14/02205-1, 16/25112-4)
LOURENCO, ESTELA MARIANA GUIMARAES; DI IORIO, JULIANA FORTES; DA SILVA, FERNANDA; FIALHO, FELIPE LEONARDO BLEY; MONTEIRO, MELQUISEDEQUE MATEUS; BEATRIZ, ADILSON; PERDOMO, RENATA TRENTIN; BARBOSA, EUZEBIO GUIMARAES; OSES, JEAN PIERRE; DE ARRUDA, CARLA CARDOZO PINTO; et al. Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis. MICROORGANISMS, v. 11, n. 1, p. 23-pg., . (21/01503-2, 16/25112-4, 14/02205-1)
JUDICE, WAGNER A. S.; FERRAZ, LETICIA SILVA; LOPES, RAYSSA DE MELLO; VIANNA, LUAN DOS SANTOS; SIQUEIRA, FABIO DA SILVA; DI IORIO, JULIANA F.; DALZOTO, LAURA DE AZEVEDO MAFFEIS; TRUJILHO, MARIANA NASCIMENTO ROMERO; SANTOS, TAIZ DOS REIS; MACHADO, MAURICIO F. M.; et al. Cysteine proteases as potential targets for anti-trypanosomatid drug discovery. Bioorganic & Medicinal Chemistry, v. 46, . (18/25747-5, 16/25112-4, 19/05936-0)
VITAL, WAGNER D.; TORQUATO, HERON F. V.; PASSOS JESUS, LARISSA DE OLIVEIRA; DE SOUZA JUDICE, WAGNER ALVES; DA SILVA, MARIA FATIMA DAS G. F.; RODRIGUES, TIAGO; JUSTO, GISELLE ZENKER; VEIGA, THIAGO A. M.; PAREDES-GAMERO, EDGAR J.. 4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines. Journal of Cellular Biochemistry, v. 120, n. 6, p. 9608-9623, . (16/18990-5, 18/04095-0, 16/25112-4)
PAPP, LUIZ ANTONIO; CARDINALI-REZENDE, JULIANA; DE SOUZA JUDICE, WAGNER ALVES; SANCHEZ, MARILIA BIXILIA; ARAUJO, WELINGTON LUIZ. Low biological phosphorus removal from effluents treated by slow sand filters. Applied Microbiology and Biotechnology, v. 106, n. 17, p. 13-pg., . (21/01503-2, 17/12510-4, 16/25112-4, 14/02205-1)
COELHO, CAMILA M.; DOS SANTOS, THIAGO; FREITAS, POLIANY G.; NUNES, JULIANA B.; MARQUES, MARCOS J.; PADOVANI, CAMILA G. D.; JUDICE, WAGNER A. S.; CAMPS, IHOSVANY; DA SILVEIRA, NELSON J. F.; CARVALHO, DIOGO T.; et al. Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Eugenol Esters as Leishmanicidal Agents. Journal of the Brazilian Chemical Society, v. 29, n. 4, p. 14-pg., . (16/25112-4)
DE NOVAIS, LEICE M. R.; DE ARUEIRA, CAUANE C. O.; FERREIRA, LUIZ F.; RIBEIRO, TEREZA A. N.; SOUSA, PAULO T., JR.; JACINTO, MARCOS J.; DE CARVALHO, MARIO G.; JUDICE, WAGNER A. S.; JESUS, LARISSA O. P.; DE SOUZA, ALINE A.; et al. 4 '-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L. Fitoterapia, v. 132, p. 4-pg., . (16/25112-4)
KAUFFMANN, ANGELICA C.; OLIVEIRA, RHAYSSA G. S. P.; DOURADO, THAINARA A.; SOARES, IURI N.; DE SOUSA, PAULO T.; RIBEIRO, TEREZA A. N.; JACINTO, MARCOS J.; DE SOUZA, GABRIEL L. C.; JUDICE, WAGNER A. DE S.; EMILIANO, MARLI DE F. C.; et al. Eleocarpanthraquinone, a novel anthraquinone from Rhamnidium elaeocarpum (Rhamnaceae). Tetrahedron Letters, v. 61, n. 45, . (16/25112-4)
DE MOURA, THALES REGGIANI; ZANETTI, RENAN DIEGO; SILVA, DEBORA EDUARDA SOARES; DE FARIAS, RENAN LIRA; MAURO, ANTONIO EDUARDO; PEREIRA, JOSE CLAYSTON MELO; DE SOUZA, ALINE APARECIDA; DA SILVA SIQUEIRA, FABIO; DE SOUZA JUDICE, WAGNER ALVES; LIMA, MAURO ALMEIDA; et al. Palladium(ii) complexes bearing 1-iminothiolate-3,5-dimethylpyrazoles: synthesis, cytotoxicity, DNA binding and enzymatic inhibition studies. NEW JOURNAL OF CHEMISTRY, v. 44, n. 45, p. 19891-19901, . (15/12098-0, 16/25112-4, 14/02205-1, 09/54011-8, 19/11242-1, 16/17711-5)
DA CUNHA, GISLAINE A.; DE SOUZA, RONAN F. F.; DE FARIAS, RENAN L.; MOREIRA, MARIETE B.; SILVA, DEBORA E. S.; ZANETTI, RENAN D.; GARCIA, DANIEL M.; SPINDOLA, DANIEL G.; MICHELIN, LUIS F. G.; BINCOLETTO, CLAUDIA; et al. Cyclopalladated compounds containing 2,6-lutidine: Synthesis, spectral and biological studies. Journal of Inorganic Biochemistry, v. 203, . (12/15486-3, 14/02205-1, 09/54011-8, 16/25112-4)
ANTUNES, ALYNE ALEXANDRINO; PASSOS JESUS, LARISSA DE OLIVEIRA; MANFREDI, MARCELLA ARAUJO; DE SOUZA, ALINE APARECIDA; MARCONDES MACHADO, MAURICIO FERREIRA; MORAES E SILVA, PAMELA; ICIMOTO, MARCELO YUDI; JULIANO, MARIA APARECIDA; JULIANO, LUIZ; DE SOUZA JUDICE, WAGNER ALVES. Thermodynamic analysis of Kex2 activity: The acylation and deacylation steps are potassium- and substrate-dependent. Biophysical Chemistry, v. 235, p. 29-39, . (14/02205-1, 15/11190-0, 16/25112-4)
JESUS, LARISSA DE OLIVEIRA PASSOS; DE SOUZA, ALINE APARECIDA; TORQUATO, HERON FERNANDES VIEIRA; GONTIJO, VANESSA SILVA; DE FREITAS, ROSSIMIRIAN PEREIRA; GESTEIRA, TARSIS FERREIRA; COULSON-THOMAS, VIVIEN JANE; TORQUATO, RICARDO JOSE SOARES; TANAKA, APARECIDA SADAE; PAREDES-GAMERO, EDGAR JULIAN; et al. In Vitro Study of Cytotoxic Mechanisms of Alkylphospholipids and Alkyltriazoles in Acute Lymphoblastic Leukemia Models. Molecules, v. 27, n. 23, p. 23-pg., . (21/01503-2, 16/25112-4, 14/02205-1)
COSTA, CLAUDIA A.; LOPES, RAYSSA M.; FERRAZ, LETICIA S.; ESTEVES, GABRIELA N. N.; DI IORIO, JULIANA F.; SOUZA, ALINE A.; DE OLIVEIRA, ISADORA M.; MANARIN, FLAVIA; JUDICE, WAGNER A. S.; STEFANI, HELIO A.; et al. Cytotoxicity of 4-substituted quinoline derivatives: Anticancer and antileishmanial potential. Bioorganic & Medicinal Chemistry, v. 28, n. 11, . (16/04289-3, 18/25747-5, 16/25112-4, 17/24821-4, 14/02205-1)
ROSA, LETICIA B.; GALUPPO, CAROLINA; LIMA, ROCHANNA L. A.; FONTES, JOSIELLE, V; SIQUEIRA, FABIO S.; JUDICE, WAGNER A. S.; ABBEHAUSEN, CAMILLA; MIGUEL, DANILO C.. Antileishmanial activity and insights into the mechanisms of action of symmetric Au(I) benzyl and aryl-N-heterocyclic carbenes. Journal of Inorganic Biochemistry, v. 229, p. 9-pg., . (14/02205-1, 19/01678-7, 16/25112-4, 18/21120-8, 19/16904-2, 14/21129-4)
LOPES, KHEYTIANY H. S.; SILVA, VIRGINIA C. P.; JACINTO, MARCOS J.; DE SOUZA, ALINE A.; PADOVANI, CAMILA G. D.; MACHADO, MAURICIO F. M.; JUDICE, WAGNER A. S.; SOUSA JR, PAULO T.. A Clerodane Diterpene from Aquarius scaber (Rataj) Christenh. & Byng leaves as Inhibitor of Leishmania mexicana Trypanosomatid Enzymes. JOURNAL OF BIOLOGICALLY ACTIVE PRODUCTS FROM NATURE, v. N/A, p. 11-pg., . (16/25112-4, 15/11190-0)
PAPP, LUIZ ANTONIO; CARDINALI-REZENDE, JULIANA; JUDICE, WAGNER ALVES DE SOUZA; SANCHES, MARILIA BIXILIA; ARAUJO, WELINGTON LUIZ. Total phosphorus contents currently found in the raw wastewater-Problems and technical solutions for its removal in full-scale wastewater treatment plants. RESOURCES CONSERVATION AND RECYCLING, v. 196, p. 10-pg., . (21/01503-2, 16/25112-4, 14/02205-1, 16/24290-6, 14/08061-1, 17/12510-4)
CARVALHO, DIEGO B.; DAS NEVES, AMARITH R.; PORTAPILLA, GISELE B.; SOARES, OZILDEIA; SANTOS, LARISSA B. B.; OLIVEIRA, JEFFERSON R. S.; VIANNA, LUAN S.; JUDICE, WAGNER A. S.; CARDOSO, IARA A.; LUCCAS, PEDRO H.; et al. Repurposing of 5-nitrofuran-3,5-disubstituted isoxazoles: A thriving scaffold to antitrypanosomal agents. ARCHIV DER PHARMAZIE, v. N/A, p. 9-pg., . (14/02205-1, 16/25112-4, 21/01503-2)

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