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Research potential against tuberculosis of a new class of furoxan compounds and nanostructured compounds of the ruthenium(II) and copper (II)

Abstract

Mycobacterium tuberculosis (MTB), agent of tuberculosis (TB), is responsible for the death of around 2-3 million people annually and a global economic toll of ~$12 billion each year. For more than 50 years after the introduction of rifampicin (RMP) in 1960, no new drug had been developed against TB. All the need of a new molecule, led to quickly TMC-207 approval by the FDA (Food and Drug Administration), which was one of the compounds in clinical phase, becoming the first drug to be used only against multidrug resistant TB (MDR-TB), called "Sirturo". Our group through many collaborations has been seeking new bioactive molecules against TB, performing the screening of more than 3,000 different compounds in the last three years. Among our background study, as objective of this study, we selected three different classes of molecules unpublished addressing two major areas of Medicinal Chemistry (inorganic and organic synthetic) that were highly promising studies both in vitro and in vivo. The challenge will be to apply all existing methodologies within our pipeline and add new methodologies that constrain the activity of compounds in all physiological profiles of susceptible and resistant MTB active beyond the state latency, virulence mechanisms, such as efflux pump machinery, metabolism and pharmacokinetic profile as well as the incorporation of compounds in microemulsions. Achieving these aims we hope indicate a new candidate(s) for anti-TB drug. (AU)

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Scientific publications (22)
(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)
CALEFFI-FERRACIOLI, KATIANY R.; CARDOSO, ROSILENE F.; DE SOUZA, JOAO V. P.; MURASE, LETICIA S.; CANEZIN, PEDRO H.; SCODRO, REGIANE B. L.; SIQUEIRA, VERA L. D.; PAVAN, FERNANDO R.. Modulatory effects of verapamil in rifampicin activity against Mycobacterium tuberculosis. FUTURE MICROBIOLOGY, v. 14, n. 3, p. 185-194, . (13/14957-5)
LARROUY-MAUMUS, GERALD; MARINO, LEONARDO B.; MADDURI, ASHOKA V. R.; RAGAN, T. J.; HUNT, DEBBIE M.; BASSANO, LUCREZIA; GUTIERREZ, MAXIMILIANO G.; MOODY, D. BRANCH; PAVAN, FERNANDO R.; DE CARVALHO, LUIZ PEDRO S.. Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis. ACS INFECTIOUS DISEASES, v. 2, n. 5, p. 352-360, . (11/21232-1, 13/14957-5)
DA SILVA, PATRICIA B.; DE SOUZA, PAULA C.; FIORAMONTI CALIXTO, GIOVANA MARIA; LOPES, ERICA DE O.; FREM, REGINA C. G.; NETTO, ADELINO V. G.; MAURO, ANTONIO E.; PAVAN, FERNANDO R.; CHORILLI, MARLUS. In Vitro Activity of Copper(II) Complexes, Loaded or Unloaded into a Nanostructured Lipid System, against Mycobacterium tuberculosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 17, n. 5, . (13/14957-5, 13/09265-7)
DOS SANTOS FERNANDES, GUILHERME FELIPE; DE SOUZA, PAULA CAROLINA; MARINO, LEONARDO BIANCOLINO; CHEGAEV, KONSTANTIN; GUGLIELMO, STEFANO; LAZZARATO, LORETTA; FRUTTERO, ROBERTA; CHUNG, MAN CHIN; PAVAN, FERNANDO ROGERIO; DOS SANTOS, JEAN LEANDRO. Synthesis and biological activity of furoxan derivatives against Mycobacterium tuberculosis. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 123, p. 523-531, . (14/24811-0, 14/11586-9, 14/02240-1, 13/14957-5)
GARCIA DE CARVALHO, NATALIA FERNANDES; SATO, DAISY NAKAMURA; PAVAN, FERNANDO R.; FERRAZOLI, LUCILAINE; CHIMARA, ERICA. Resazurin Microtiter Assay for Clarithromycin Susceptibility Testing of Clinical Isolates of Mycobacterium abscessus Group. JOURNAL OF CLINICAL LABORATORY ANALYSIS, v. 30, n. 5, p. 751-755, . (13/14957-5)
DE FREITAS, EDUARDO SINESIO; DA SILVA, PATRICIA BENTO; CHORILLI, MARLUS; BATISTA, ALZIR AZEVEDO; LOPES, ERICA DE OLIVEIRA; DA SILVA, MONIZE MARTINS; FUJIMURA LEITE, CLARICE QUEICO; PAVAN, FERNANDO ROGERIO. Nanostructured Lipid Systems as a Strategy to Improve the in Vitro Cytotoxicity of Ruthenium(II) Compounds. Molecules, v. 19, n. 5, p. 5999-6008, . (13/14957-5, 13/09265-7)
DE SOUZA, P. C.; FERNANDES, G. F. S.; MARINO, L. B.; RIBEIRO, C. M.; DA SILVA, P. B.; CHORILLI, M.; SILVA, C. S. P.; RESENDE, F. A.; SOLCIA, M. C.; DE GRANDIS, R. A.; et al. Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection. BIOMEDICINE & PHARMACOTHERAPY, v. 130, . (18/11079-0, 18/00163-0, 14/03920-6, 17/12419-7, 16/09502-7, 14/02240-1, 13/14957-5, 16/02860-5, 14/24811-0, 16/24633-0, 18/17739-2, 15/19531-1, 16/22429-7, 14/11586-9)
MCCARRON, PAURAIC; MCCANN, MALACHY; DEVEREUX, MICHAEL; KAVANAGH, KEVIN; SKERRY, CIARAN; KARAKOUSIS, PETROS C.; AOR, ANA C.; MELLO, THAIS P.; SANTOS, ANDRE L. S.; CAMPOS, DEBORA L.; et al. Unprecedented in Vitro Antitubercular Activitiy of Manganese(II) Complexes Containing 1,10-Phenanthroline and Dicarboxylate Ligands: Increased Activity, Superior Selectivity, and Lower Toxicity in Comparison to Their Copper(II) Analogs. FRONTIERS IN MICROBIOLOGY, v. 9, . (13/14957-5)
FERNANDES, LAISA DE P.; SILVA, JULIA M. B.; MARTINS, DANIEL O. S.; SANTIAGO, MARIANA B.; MARTINS, CARLOS H. G.; JARDIM, ANA C. G.; OLIVEIRA, GUEDMILLER S.; PIVATTO, MARCOS; SOUZA, RAFAEL A. C.; FRANCA, EDUARDO DE F.; et al. Fragmentation Study, Dual Anti-Bactericidal and Anti-Viral Effects and Molecular Docking of Cobalt(III) Complexes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 21, . (09/54011-8, 13/14957-5, 11/16380-1)
CAMPOS, DEBORA L.; MACHADO, IGNACIO; RIBEIRO, CAMILA M.; GAMBINO, DINORAH; PAVAN, FERNANDO R.. Bactericidal effect of pyridine-2-thiol 1-oxide sodium salt and its complex with iron against resistant clinical isolates of Mycobacterium tuberculosis. JOURNAL OF ANTIBIOTICS, v. 73, n. 2, p. 120-124, . (13/14957-5, 18/00163-0)
DA SILVA, PATRICIA BENTO; SOUSA ARAUJO, VICTOR HUGO; FONSECA-SANTOS, BRUNO; SOLCIA, MARIANA CRISTINA; RIBEIRO, CAMILA MARINGOLO; DA SILVA, ISABEL CRISTIANE; ALVES, RENATA CAROLINA; PIRONI, ANDRESSA MARIA; LOPES SILVA, ANA CAROLINA; VICTORELLI, FRANCESCA DAMIANI; et al. Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization. Current Medicinal Chemistry, v. 28, n. 10, p. 1906-1956, . (17/10016-2, 13/14957-5, 18/00163-0)
FERNANDES, ANDRE G. DE A.; VIANA, ROMMEL B.; MORENO-FUQUEN, RODOLFO; GATTO, CLAUDIA C.; LANG, ERNESTO S.; MODOLO, MARCEL Z.; SILVA, AMANDHA K.; LEMOS, SEBASTIAO S.; HAGENBACH, ADELHEID; ABRAM, ULRICH; et al. xorhenium(V) complexes with a benzyldithiocarbazate ligand: synthesis, crystal structure, spectroscopic and DFT analyse. Journal of Molecular Structure, v. 1250, n. 3, . (12/19175-2, 13/14957-5, 09/54011-8)
DE SOUZA, PAULA C.; MAIA, PEDRO I. S.; DE BARROS, HELOISA B.; LEITE, CLARICE Q. F.; DEFLON, VICTOR M.; PAVAN, FERNANDO R.. Vanadium Complexes with Hydrazone or Thiosemicarbazone Ligands as Potential Anti-Mycobacterium tuberculosis Agents. CURRENT CLINICAL PHARMACOLOGY, v. 10, n. 1, p. 66-72, . (09/54011-8, 13/14957-5, 14/11586-9)
DA SILVA, PATRICIA BENTO; CAMPOS, DEBORA LEITE; RIBEIRO, CAMILA MARINGOLO; DA SILVA, ISABEL CRISTIANE; PAVAN, FERNANDO ROGERIO. New antimycobacterial agents in the pre-clinical phase or beyond: recent advances in patent literature (2001-2016). EXPERT OPINION ON THERAPEUTIC PATENTS, v. 27, n. 3, p. 269-282, . (13/14957-5)
DOS SANTOS FERNANDES, GUILHERME FELIPE; DE SOUZA, PAULA CAROLINA; MORENO-VIGURI, ELSA; SANTIVANEZ-VELIZ, MERY; PAUCAR, ROCIO; PEREZ-SILANES, SILVIA; CHEGAEV, KONSTANTIN; GUGLIELMO, STEFANO; LAZZARATO, LORETTA; FRUTTERO, ROBERTA; et al. Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity. Journal of Medicinal Chemistry, v. 60, n. 20, p. 8647-8660, . (14/02240-1, 13/14957-5, 14/03920-6, 14/24811-0, 15/19531-1, 14/11586-9, 16/02860-5, 16/09502-7)
DOS SANTOS FERNANDES, GUILHERME FELIPE; JORNADA, DANIELA HARTMANN; DE SOUZA, PAULA CAROLINA; CHIN, CHUNG MAN; PAVAN, FERNANDO ROGERIO; DOS SANTOS, JEAN LEANDRO. Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets. Current Medicinal Chemistry, v. 22, n. 27, p. 3133-3161, . (14/24811-0, 13/14957-5, 14/02240-1)
DA SILVA, PATRICIA B.; DE FREITAS, EDUARDO SINESIO; SOLCIA, MARIANA CRISTINA; DE SOUZA, PAULA CAROLINA; DA SILVA, MONIZE MARTINS; BATISTA, ALZIR AZEVEDO; EISMANN, CARLOS E.; ROLISOLA, ANA MARTA C. M.; MENEGARIO, AMAURI A.; CARDOSO, ROSILENE FRESSATTI; et al. A Nanostructures Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis. FRONTIERS IN MICROBIOLOGY, v. 9, . (13/14957-5, 13/09265-7)
DA SILVA, PATRICIA BENTO; DE FREITAS, EDUARDO SINESIO; BERNEGOSSI, JESSICA; GONCALEZ, MAIRA LIMA; SATO, MARIANA RILLO; FUJIMURA LEITE, CLARICE QUEICO; PAVAN, FERNANDO ROGERIO; CHORILLI, MARIUS. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis-A Review. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v. 12, n. 2, p. 241-260, . (12/19568-4, 13/14957-5, 13/09265-7)
DA SILVA, PATRICIA B.; BONIFACIO, BRUNA V.; FREM, REGINA C. G.; GODOY NETTO, ADELINO V.; MAURO, ANTONIO E.; DA COSTA FERREIRA, ANA M.; LOPES, ERICA DE O.; RADDI, MARIA S. G.; BAUAB, TAIS M.; PAVAN, FERNANDO R.; et al. A Nanostructured Lipid System as a Strategy to Improve the in Vitro Antibacterial Activity of Copper(II) Complexes. Molecules, v. 20, n. 12, p. 22534-22545, . (13/14957-5, 13/09265-7)
PLUTIN, ANA M.; ALVAREZ, ANISLAY; MOCELO, RAUL; RAMOS, RAUL; CASTELLANO, EDUARDO E.; DA SILVA, MONIZE M.; COLINA-VEGAS, LEGNA; PAVAN, FERNANDO R.; BATISTA, ALZIR A.. Anti-Mycobacterium tuberculosis activity of platinum(II)/N,N-disubstituted-N `-acyl thiourea complexes. Inorganic Chemistry Communications, v. 63, p. 74-80, . (14/13691-4, 13/14957-5)
CORREIA, ISABEL; ADAO, PEDRO; ROY, SOMNATH; WAHBA, MOHAMED; MATOS, CRISTINA; MAURYA, MANNAR R.; MARQUES, FERNANDA; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; AVECILLA, FERNANDO; et al. Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as potential anti-tuberculosis and anti-tumor agents. Journal of Inorganic Biochemistry, v. 141, p. 83-93, . (13/14957-5)
ELAINE S. COIMBRA; JULIANA A. SANTOS; LARISSA L. LIMA; PATRÍCIA A. MACHADO; DÉBORA L. CAMPOS; FERNANDO R. PAVAN; ADILSON D. SILVA. Synthesis, Antitubercular and Leishmanicidal Evaluation of Resveratrol Analogues. Journal of the Brazilian Chemical Society, v. 27, n. 12, p. 2161-2169, . (13/14957-5)

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