Synthesis, characterization and studies of interaction with biomolecules of metal complexes containing biologically active ligands: a strategy in the preparation of new agents with antibacterial and antiviral activities

• Grant number: 18/12062-4
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2018 - May 31, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Pedro Paulo Corbi
• Grantee: Pedro Paulo Corbi
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Several diseases caused by bacteria of different species, as well as those caused by some types of viruses, such as influenza and dengue, are a case of concern. Epidemiological data estimate 3 to 5 million cases of influenza per year and approximately 290 to 650 thousand deaths. The symptoms caused by severe cases of influenza are similar to the symptoms caused by dengue fever, which is a viral infection transmitted by mosquitoes and can cause severe complications. Dengue fever has been increasing progressively in recent decades and an estimated 390 million cases are reported each year in more than 100 countries, exposing nearly half of the world's population to a situation of risk. In the search for new pharmacologically active complexes, a particular interest has been given to the interaction of metals with already known and established antibacterial drugs, such as sulfonamides, and with those used as antivirals such as adamantane derivatives. Thus, the combination of biologically active ligands and metals of well-known antimicrobial action may result in novel drug candidates with differentiated mechanisms of action and activities on microorganisms at different stages of cell growth. Such compounds could also lead to a decrease in the possibility of the emergence of microbial resistance when compared to free drugs. In this project, the synthesis and characterization of Ag(I), Cu(II), Pt(II) and Pd(II) complexes with the sulfonamides mafenide and sulfamethazine will be discussed, as well as the preparation of complexes with adamantane derivatives , such as rimantadine and amantadine. The complexes will be characterized by a set of chemical and spectroscopic techniques, with emphasis on infrared and nuclear magnetic resonance spectroscopic measurements, X-ray diffraction of single-crystals and high-resolution mass spectrometry. The compounds will be evaluated for their antibacterial activities on a set of Gram-positive and Gram-negative strains, determining the minimum inhibitory concentration values, with emphasis on the action on Mycobacterium tuberculosis. Antiviral activities, especially on species that cause diseases such as influenza, dengue, zika and chikungunya will be evaluated by the molecular RT-PCR method, quantifying the viral loads. Subsequently, cytotoxicity studies on different cell types will be performed to evaluate the safety, selectivity and potential of application of the compounds of interest. The active compounds will be submitted to procedures of interaction with biomolecules such as DNA and proteins to evaluate their potential biological targets. (AU)

Scientific publications

(14)

(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)

DOS SANTOS PEREIRA, ANNA KARLA; NAKAHATA, DOUGLAS HIDEKI; MANZANO, CARLOS MARROTE; SIMONI, DEBORAH DE ALENCAR; PEREIRA, DOUGLAS HENRIQUE; LUSTRI, WILTON ROGERIO; BARBOZA FORMIGA, ANDRE LUIZ; CORBI, PEDRO PAULO. Synthesis, crystallographic studies, molecular modeling and in vitro biological studies of silver(I) complexes with aminoadamantane ligands. Polyhedron, v. 173, NOV 15 2019. (15/20882-3, 14/50906-9, 18/12062-4, 13/22127-2, 17/25995-6, 18/12590-0)

MANZANO, CARLOS M.; NAKAHATA, DOUGLAS H.; TENORIO, JUAN C.; LUSTRI, WILTON R.; RESENDE NOGUEIRA, FLAVIA A.; ALEIXO, NADIA A.; DA SILVA GOMES, PIETRA S.; PAVAN, FERNANDO R.; GRECCO, JULIA A.; RIBEIRO, CAMILA M.; et al. Silver complexes with fluoroanthranilic acid isomers: Spectroscopic characterization, antimycobacterial activity and cytotoxic studies over a panel of tumor cells. Inorganica Chimica Acta, v. 502, MAR 1 2020. (18/00163-0, 18/12062-4, 17/16278-9, 17/25995-6)

BORMIO NUNES, JULIA H.; DE PAIVA, PAULA P.; RUIZ, ANA LUCIA T. G.; DE CARVALHO, JOAO ERNESTO; CORBI, PEDRO P.. New findings on the antiproliferative activity of the silver(I) complex with 5-fluorouracil against human multi-resistant NCI/ADR-RES ovarian tumor cells. TOXICOLOGY IN VITRO, v. 60, p. 359-368, OCT 2019. (18/12062-4, 15/25114-4)

DOS SANTOS PEREIRA, ANNA KARLA; MANZANO, CARLOS MARROTE; NAKAHATA, DOUGLAS HIDEKI; TENORIO CLAVIJO, JUAN CARLOS; PEREIRA, DOUGLAS HENRIQUE; LUSTRI, WILTON ROGERIO; CORBI, PEDRO PAULO. Synthesis, crystal structures, DFT studies, antibacterial assays and interaction assessments with biomolecules of new platinum(ii) complexes with adamantane derivatives. NEW JOURNAL OF CHEMISTRY, v. 44, n. 27, p. 11546-11556, JUL 21 2020. (13/08293-7, 17/11485-6, 15/20882-3, 18/12590-0, 17/25995-6, 18/12062-4)

FIORI-DUARTE, ANA THEREZA; BERGAMINI, FERNANDO R. G.; DE PAIVA, RAPHAEL ENOQUE E.; MANZANO, CARLOS M.; LUSTRI, WILTON R.; CORBI, PEDRO P.. A new palladium(II) complex with ibuprofen: Spectroscopic characterization, DFT studies, antibacterial activities and interaction with biomolecules. Journal of Molecular Structure, v. 1186, p. 144-154, JUN 15 2019. (18/12062-4, 15/25114-4, 10/00667-7, 17/25995-6, 15/09833-0)

FIORI-DUARTE, ANA THEREZA; DE PAIVA, RAPHAEL ENOQUE F.; MANZANO, CARLOS M.; LUSTRI, WILTON R.; CORBI, PEDRO P.. Silver(I) and gold(I) complexes with sulfasalazine: Spectroscopic characterization, theoretical studies and antiproliferative activities over Gram-positive and Gram-negative bacterial strains. Journal of Molecular Structure, v. 1214, AUG 15 2020. (18/12062-4, 18/12590-0, 17/25995-6, 15/09833-0)

ESQUEZARO, PEDRO GONCALVES; MANZANO, CARLOS MARROTE; NAKAHATA, DOUGLAS HIDEKI; SANTOS, IGOR ANDRADE; AQUINO RUIZ, URIEL ENRIQUE; SANTIAGO, MARIANA BRENTINI; SOUZA SILVA, NAGELA BERNADELLI; GOMES MARTINS, CARLOS HENRIQUE; PEREIRA, DOUGLAS HENRIQUE; GOULART BERGAMINI, FERNANDO RODRIGUES; et al. Synthesis, spectroscopic characterization and in vitro antibacterial and antiviral activities of novel silver(I) complexes with mafenide and ethyl-mafenide. Journal of Molecular Structure, v. 1246, DEC 15 2021. (18/12062-4, 17/25995-6, 17/11485-6, 13/08293-7)

GOMES TELES, RAMON HANDERSON; GRAMINHA, ANGELICA ELLEN; RIVERA-CRUZ, COSETTE M.; NAKAHATA, DOUGLAS HIDEKI; BARBOZA FORMIGA, ANDRE LUIZ; CORBI, PEDRO PAULO; FIGUEIREDO, MARXA LEAO; COMINETTI, MARCIA REGINA. Copper transporter 1 affinity as a delivery strategy to improve the cytotoxic profile of rationally designed copper(II) complexes for cancer treatment. TOXICOLOGY IN VITRO, v. 67, SEP 2020. (18/12062-4, 15/20882-3, 18/17170-0, 13/07600-3, 17/19504-0)

PARIS JUNIOR, JOSE ALBERTO; CAVICCHIOLI, MAURICIO; AMARAL MACHADO, RACHEL TEMPERANI; PAVAN, FERNANDO; NAKAHATA, DOUGLAS HIDEKI; CORBI, PEDRO PAULO; FERREIRA COSTA, ADAO MARCOS; PEREIRA, DOUGLAS HENRIQUE; MASSABNI, ANTONIO CARLOS. SYNTHESIS, CHARACTERIZATION, DFT MODELING AND IN VITRO ANTIMYCOBACTERIAL ACTIVITY ASSAYS OF A SILVER(I)-ISONIAZID COMPLEX. Química Nova, v. 44, n. 3, p. 278-283, 2021. (13/08293-7, 15/20882-3, 17/11570-3, 17/11485-6, 18/12062-4)

QUINTANILHA, MARIANA MAZZO; SCHIMITD, BIANCA ALVES; COSTA, ADAO MARCOS FERREIRA; NAKAHATA, DOUGLAS HIDEKI; SIMONI, DEBORAH DE ALENCAR; CLAVIJO, JUAN CARLOS TENORIO; PEREIRA, DOUGLAS HENRIQUE; MASSABNI, ANTONIO CARLOS; LUSTRI, WILTON ROGERIO; CORBI, PEDRO PAULO. A novel water-soluble platinum(II) complex with the amino acid deoxyalliin: synthesis, crystal structure, theoretical studies and investigations about its antibacterial activity. Journal of Molecular Structure, v. 1236, JUL 15 2021. (13/08293-7, 15/20882-3, 18/09860-6, 18/09856-9, 18/12590-0, 15/09833-0, 18/12062-4, 17/11485-6)

DOS SANTOS, PAULO VICTOR P.; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; CORBI, PEDRO P.; BERGAMINI, FERNANDO R. G.; CARVALHO, MARCOS A.; D'OLIVERIA, KAIQUE A.; CUIN, ALEXANDRE. Promising Ag(I) complexes with N-acylhydrazones from aromatic aldehydes and isoniazid against multidrug resistance in tuberculosis. Journal of Molecular Structure, v. 1234, JUN 15 2021. (18/12062-4, 18/00163-0)

DOS SANTOS PEREIRA, ANNA KARLA; SANTOS, IGOR A.; DA SILVA, WASHINGTON W.; RESENDE NOGUEIRA, FLAVIA A.; BERGAMINI, FERNANDO R. G.; JARDIM, ANA CAROLINA G.; CORBI, PEDRO P.. Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?. PHARMACOLOGICAL REPORTS, v. 73, n. 3, FEB 2021. (18/12062-4, 17/16278-9)

DE PAIVA, RAPHAEL E. F.; NETO, ANTONIO MARCAL; SANTOS, IGOR A.; JARDIM, ANA C. G.; CORBI, PEDRO P.; BERGAMINI, FERNANDO R. G.. What is holding back the development of antiviral metallodrugs? A literature overview and implications for SARS-CoV-2 therapeutics and future viral outbreaks. DALTON TRANSACTIONS, v. 49, n. 45, p. 16004-16033, DEC 7 2020. (18/12062-4, 18/21537-6)

SIMEI AQUARONI, NAYARA AP.; NAKAHATA, DOUGLAS H.; LAZARINI, SILMARA C.; RESENDE, FLAVIA A.; CANDIDO, AMANDA L. P.; BARUD, HERNANE DA SILVA; CLARO, AMANDA MARIA; DE CARVALHO, JOAO ERNESTO; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. Journal of Inorganic Biochemistry, v. 212, NOV 2020. (17/19243-1, 15/09833-0, 17/16278-9, 18/12062-4, 16/07729-4, 13/07276-1, 18/12590-0, 18/25512-8, 14/06779-2, 19/03049-7, 18/02344-2, 18/00163-0, 15/20882-3)