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

• Grant number: 13/14957-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2014
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Fernando Rogério Pavan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Alzir Azevedo Batista ; Clarice Queico Fujimura Leite ; Jean Leandro dos Santos ; Marlus Chorilli
• Associated scholarship(s): 15/24632-1 - Evaluation of a. salina as a toxicity alternative method in antibiotics used against tuberculosis, BP.IC; 15/02011-5 - Evaluation of in vitro and in vivo activity of thiosemicarbazones compounds encapsulated in lipid microemulsions utilizing nanotechnology, BP.PD; 15/00077-9 - Study of MIC, MBC and time-kill kinects of 2-mercaptopyridine N-oxide sodium salt (Nampo) and and its corresponding complex [Fe(mpo)3] against different strains of Mycobacterium tuberculosis, BP.IC; 14/11586-9 - Studies in vitro and in vivo of furoxan compounds with potential application for the treatment of tuberculosis, BP.DR; 14/03920-6 - Evaluation of pharmacological interaction and bactericidal kinetics of new furoxanic molecules in combination with rifampicin, isoniazid, amikacin, and moxifloxacin against Mycobacterium tuberculosis H37Rv, BP.IC

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 Among our background study, as objective of this study, we selected three different classes of molecules unpublished addressing two major areas of Medicinal Chemistry (inorganic and organic synthetic) that were highly promising studies both in vitro and in vivo.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)

Scientific publications

(25)

(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)

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, JAN 2016. (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, DEC 2014. (13/14957-5)

OLIVEIRA, CAROLINA G.; MAIA, PEDRO IVO DA S.; MIYATA, MARCELO; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; DE ALMEIDA, EDUARDO TONON; DEFLON, VICTOR M.. Cobalt(III) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents. Journal of the Brazilian Chemical Society, v. 25, n. 10, p. 1848+, OCT 2014. (11/16380-1, 09/54011-8, 13/14957-5)

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, 2015. (14/24811-0, 14/02240-1, 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, 2016-12-00. (13/14957-5)

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, MAR 2017. (13/14957-5)

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, 2015. (09/54011-8, 13/14957-5, 14/11586-9)

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, FEB 2016. (12/19568-4, 13/09265-7, 13/14957-5)

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, DEC 2015. (13/09265-7, 13/14957-5)

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, DEC 6 2018. (13/09265-7, 13/14957-5)

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, FEB 15 2022. (12/19175-2, 13/14957-5, 09/54011-8)

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, OCT 26 2017. (15/19531-1, 13/14957-5, 14/24811-0, 14/11586-9, 14/03920-6, 16/09502-7, 16/02860-5, 14/02240-1)

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, 2021. (18/00163-0, 17/10016-2, 13/14957-5)

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, FEB 2020. (18/00163-0, 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, NOV 2020. (11/16380-1, 09/54011-8, 13/14957-5)

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, FEB 2019. (13/14957-5)

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, NOV 10 2016. (14/11586-9, 14/24811-0, 14/02240-1, 13/14957-5)

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, JUL 2 2018. (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, SEP 2016. (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, MAY 2016. (13/09265-7, 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, MAY 2016. (13/14957-5, 11/21232-1)

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, MAY 2014. (13/09265-7, 13/14957-5)

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, OCT 2020. (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)

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 Nanostructured Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis (vol 9, 2930, 2018). FRONTIERS IN MICROBIOLOGY, v. 10, p. 1-pg., 2019-05-31. (13/09265-7, 13/14957-5)

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. 7-pg., 2016-01-01. (13/14957-5, 14/13691-4)