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New Ag(I), Pd(II) and Pt(II) metal complexes with ligands used for the treatment of Tuberculosis: synthesis and in vitro evaluation of antimicrobial and antiproliferative activities

Grant number: 17/25995-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2018
Effective date (End): February 28, 2022
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Pedro Paulo Corbi
Grantee:Carlos Marrote Manzano
Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


The increasing bacterial resistance to antibiotics is a global concern that urges the development of new drugs to treat serious infections. Tuberculosis is caused by the bacteria Mycobacterium tuberculosis. One of the reasons for the high mortality number caused by tuberculosis is the emergence of many new bacterial stains that are multiresistant to first line commercial drugs. One strategy to fight multiresistant bacteria is to coordinate well-known drugs to a metal ion with antibacterial activity, resulting in a coordination compound that would have additive or synergic activity with the ligand. Metal complexes with Ag(I) or Pt(II) ions are known for their antibacterial and antitumoral properties, that can be exemplified by silver sulphadiazine, used for the treatment of skin bacterial infections, and cisplatin, used for Cancer chemotherapy and that also has considerable antimicrobial activity. These and other metal ions have been considered for the development of new complexes as lead drugs by research groups. In that context, this project aims at the synthesis, optimization and characterization of new Ag(I), Pd(II) and Pt(II) complexes using as ligand the drugs D-cycloserine and kanamycin A, that are used for Tuberculosis therapy, and also some derivatives of anthranilic acid that have high activity against Mycobacterium tuberculosis. The activity of the complexes against Mycobacterium tuberculosis, as well as the inhibition of eukaryotic cells proliferation using tumoral and non-tumoral cell lines will be evaluated. Furthermore, in this project we also envisage the study of the interaction of the complexes with some biomolecules to suggest their biological mechanism of action. With these assays we hope to determine the pharmacological potential of Ag(I), Pt(II) and Pd(II) complexes to treat severe infectious diseases, as Tuberculosis, and also for Cancer chemotherapy. (AU)

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Scientific publications (9)
(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, . (15/20882-3, 14/50906-9, 18/12062-4, 13/22127-2, 17/25995-6, 18/12590-0)
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, . (13/08293-7, 17/11485-6, 15/20882-3, 18/12590-0, 17/25995-6, 18/12062-4)
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, . (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, . (18/12062-4, 17/25995-6, 17/11485-6, 13/08293-7)
MANZANO, CARLOS M.; NAKAHATA, DOUGLAS H.; DE PAIVA, RAPHAEL E. F.. Revisiting metallodrugs for the treatment of skin cancers. Coordination Chemistry Reviews, v. 462, p. 71-pg., . (18/21537-6, 17/25995-6)
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, . (18/00163-0, 18/12062-4, 17/16278-9, 17/25995-6)
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, . (18/12062-4, 15/25114-4, 10/00667-7, 17/25995-6, 15/09833-0)
BERGAMINI, FERNANDO R. G.; NUNES, JULIA H. B.; MANZANO, CARLOS MARROTE; DE CARVALHO, MARCOS ALBERTO; RIBEIRO, MARCOS ANTONIO; RUIZ, ANA LUCIA TASCA GOIS; DE CARVALHO, JOAO ERNESTO; LUSTRI, WILTON ROGERIO; DE PAIVA, RAPHAEL ENOQUE FERRAZ; PORTES, MARCELO CECCONI; et al. Investigating the antiproliferative activities of new Cu-II complexes with pyridine hydrazone derivatives of nalidixic acid. Journal of Inorganic Biochemistry, v. 234, p. 11-pg., . (21/08717-8, 13/07937-8, 18/12590-0, 17/25995-6, 15/25114-4, 18/12062-4)
OLIVEIRA, IGOR SANTOS; MANZANO, CARLOS MARROTE; NAKAHATA, DOUGLAS HIDEKI; SANTIAGO, MARIANA BRENTINI; SILVA, NAGELA BERNADELLI SOUSA; MARTINS, CARLOS HENRIQUE GOMES; RESPINDULA, FERNANDO PIMENTEL; PEREIRA, DOUGLAS HENRIQUE; CORBI, PEDRO PAULO. Antibacterial and antifungal activities in vitro of a novel silver(I) complex with sulfadoxine-salicylaldehyde Schiff base. Polyhedron, v. 225, p. 12-pg., . (17/25995-6, 18/12062-4, 21/08717-8)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MANZANO, Carlos Marrote. Novos complexos metálicos com derivados do ácido antranílico e cicloserina: síntese, caracterização e avaliação de suas atividades biológicas. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Química Campinas, SP.

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