Metal complexes of sulfamethoxydiazine and sulfadimethoxine: synthesis, characterization and applications as antimicrobial agents for topical use

• Grant number: 15/20882-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2016
• Effective date (End): December 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Pedro Paulo Corbi
• Grantee: Douglas Hideki Nakahata
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 18/01451-0 - Functionalization of polynuclear platinum(II) complexes with sulfonamides for development of novel anticancer agents, BE.EP.DR

Abstract

The discovery of the antibacterial activities of sulfonamides and their applications in the treatment of infections resulted in an increase of life time and reduction of human mortality. However, their indiscriminate use led to the appearance of multiresistant bacterial strains, making the search for new drugs an important area of research. One of the strategies for the development of new antibacterial drugs is the modification of existing molecules. The Schiff bases from sulfonamides constitute a promising class of molecules for the treatment of bacterial infections. Beyond the modification of the free sulfonamides, there is also the possibility of combining the existing sulfonamides with metals that possess recognized antibacterial activities, such as copper, silver, palladium and platinum, aiming synergistic effects and the obtention of new compounds active against multiresistant strains. In this context, this project aims the synthesis of new metal complexes with two sulfonamides, sulfamethoxydiazine and sulfadimetoxina, and their Schiff bases. The ligands and the respective complexes will be synthesized in aqueous or alcoholic solutions and characterized by a set of chemical and spectroscopic analyses, with emphasis to nuclear magnetic resonance spectroscopy of 1H, 13C and {15N,1H} and high resolution mass spectrometry. The antibacterial activities of the compounds will be initially evaluated by the disc diffusion method (antibiogram). Afterwards, the active compounds will have their minimum inhibitory concentration determined over both Gram-positive (S. aureus and E. faecalis) and Gram-negative (P. aeruginosa and E. coli). Citotoxicity studies of the sulfonamides and the complexes will be performed over different cell lines in order to evaluate their selectivity and the potential of topical application for the treatment of skin infections. (AU)

Scientific publications

(21)

(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)

FIORI, ANA THEREZA M.; NAKAHATA, DOUGLAS H.; CUIN, ALEXANDRE; LUSTRI, WILTON R.; CORBI, PEDRO P.. Synthesis, crystallographic studies, high resolution mass spectrometric analyses and antibacterial assays of silver(I) complexes with sulfisoxazole and sulfadimethoxine. Polyhedron, v. 121, p. 172-179, JAN 10 2017. (15/09833-0, 15/25114-4, 15/20882-3)

NAKAHATA, DOUGLAS H.; LUSTRI, WILTON R.; CUIN, ALEXANDRE; CORBI, PEDRO P.. Crystal structure, spectroscopic characterization and antibacterial activities of a silver complex with sulfameter. Journal of Molecular Structure, v. 1125, p. 609-615, DEC 5 2016. (15/09833-0, 15/25114-4, 15/20882-3)

DE PAIVA, RAPHAEL E. F.; DU, ZHIFENG; NAKAHATA, DOUGLAS H.; LIMA, FREDERICO A.; CORBI, PEDRO P.; FARRELL, NICHOLAS P.. Gold-Catalyzed C-S Aryl-Group Transfer in Zinc Finger Proteins. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v. 57, n. 30, p. 9305-9309, JUL 20 2018. (15/25114-4, 15/20882-3)

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)

NAKAHATA, DOUGLAS H.; DE PAIVA, RAPHAEL E. F.; LUSTRI, WILTON R.; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; DA SILVA, GISELE G.; RUIZ, ANA L. T. G.; DE CARVALHO, JOAO E.; CORBI, PEDRO P.. Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities. Journal of Inorganic Biochemistry, v. 187, p. 85-96, OCT 2018. (15/09833-0, 15/25114-4, 15/20882-3)

NAKAHATA, DOUGLAS H.; DE PAIVA, RAPHAEL E. F.; LUSTRI, WILTON R.; CORBI, PEDRO P.. Sulfonamide-containing copper(ii) complexes: new insights on biophysical interactions and antibacterial activities. NEW JOURNAL OF CHEMISTRY, v. 44, n. 40, p. 9-pg., 2020-10-28. (15/09833-0, 15/20882-3, 18/12062-4, 18/21537-6, 18/12590-0, 15/25114-4)

FERRAZ DE PAIVA, RAPHAEL ENOQUE; NAKAHATA, DOUGLAS HIDEKI; DE CARVALHO, MARCOS ALBERTO; GOULART BERGAMINI, FERNANDO RODRIGUES; CORBI, PEDRO PAULO. N,N ',N '' versus N,N ',O imine-containing coordination motifs: ligand-directed synthesis of mono-nuclear and binuclear Cu-II compounds. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, p. 14-pg., 2017-10-01. (15/20882-3, 15/25114-4)

SIMEI AQUARONI, NAYARA APARECIDA; NAKAHATA, DOUGLAS HIDEKI; CORBI, PEDRO PAULO; LUSTRI, WILTON ROGERIO. Antibacterial activities of a Ag(I) complex with 4-aminobenzoic acid. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 22, p. 1-pg., 2017-07-01. (15/20882-3, 15/25114-4, 15/09833-0)

FERRAZ DE PAIVA, RAPHAEL ENOQUE; NAKAHATA, DOUGLAS HIDEKI; CORBI, PEDRO PAULO. Synthesis and crystal structure of dichlorido(1,10-phenanthroline-kappa N-2,N ')gold(III) hexafluoridophosphate. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, p. 8-pg., 2017-07-01. (15/20882-3, 15/25114-4)

FERRAZ DE PAIVA, RAPHAEL ENOQUE; NAKAHATA, DOUGLAS HIDEKI; DE CARVALHO, MARCOS ALBERTO; GOULART BERGAMINI, FERNANDO RODRIGUES; CORBI, PEDRO PAULO. N,N `,N `' versus N,N `,O imine-containing coordination motifs: ligand-directed synthesis of mono-nuclear and binuclear Cu-II compounds. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 10, p. 1563+, OCT 2017. (15/25114-4, 15/20882-3)

FERRAZ DE PAIVA, RAPHAEL ENOQUE; NAKAHATA, DOUGLAS HIDEKI; CORBI, PEDRO PAULO. Synthesis and crystal structure of dichlorido(1,10-phenanthroline-kappa N-2,N `)gold(III) hexafluoridophosphate. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 73, n. 7, p. 1048+, JUL 2017. (15/25114-4, 15/20882-3)

NUNES, JULIA H. B.; NAKAHATA, DOUGLAS H.; LUSTRI, WILTON R.; CORBI, PEDRO P.; DE PAIVA, RAPHAEL E. F.. The nitro-reduced metabolite of nimesulide: Crystal structure, spectroscopic characterization, ESI-QTOF mass spectrometric analysis and antibacterial evaluation. Journal of Molecular Structure, v. 1157, p. 469-475, APR 5 2018. (15/09833-0, 12/21955-6, 15/20882-3)

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)

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)

NAKAHATA, DOUGLAS HIDEKI; FERRAZ DE PAIVA, RAPHAEL ENOQUE; LUSTRI, WILTON ROGERIO; RIBEIRO, CAMILA MARINGOLO; PAVAN, FERNANDO ROGERIO; CORBI, PEDRO PAULO. Copper(II) complexes with sulfonamides: crystal structures, biophysical assays and antimycobacterial activity. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, v. 22, p. 1-pg., 2017-07-01. (15/20882-3, 15/25114-4, 15/09833-0)

DOUGLAS H. NAKAHATA; CARLOS E. S. P. CORSINO; GUILHERME C. DE MORAIS; GABRIELE M. PEREIRA; ÁLLEFE B. CRUZ; DOUGLAS HENRIQUE PEREIRA; NATASHA M. CASSANI; URIEL ENRIQUE A. RUIZ; IGOR A. SANTOS; ANA CAROLINA G. JARDIM; et al. Synthesis, Characterization and in vitro Evaluation of 4-(2-Aminoethyl)benzenesulfonamide Schiff Bases against Arboviruses. Journal of the Brazilian Chemical Society, v. 35, n. 11, 2024-05-10. (13/08293-7, 17/11485-6, 15/20882-3, 21/10265-8)

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)

LUSTRI, WILTON R.; LAZARINI, SILMARA C.; AQUARONI, NAYARA AP SIMEI; RESENDE, FLAVIA A.; ALEIXO, NADIA A.; PEREIRA, DOUGLAS H.; LUSTRI, BRUNA CARDINALI; MOREIRA, CRISTIANO GALLINA; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. A new complex of silver(I) with probenecid: Synthesis, characterization, and studies of antibacterial and extended spectrum beta-lactamases (ESBL) inhibition activities. Journal of Inorganic Biochemistry, v. 243, p. 12-pg., 2023-03-30. (18/00163-0, 19/03049-7, 15/09833-0, 15/20882-3, 18/12062-4, 17/16278-9, 21/07458-9, 17/19243-1, 20/13497-4, 18/12590-0, 19/26696-8, 18/00187-7, 21/08717-8, 18/02344-2)

SANTA CRUZ HUAMANI, LUIS ENRIQUE; TENORIO, JUAN CARLOS; GUERRA, RENAN BARRACH; NAKAHATA, DOUGLAS HIDEKI; BIBI, NAHEED; BONACIN, JULIANO ALVES; BARBOZA FORMIGA, ANDRE LUIZ. Role of Protonation and Isomerism in the Supramolecular Architectures of Heteroaryl-2-imidazole Compounds: Crystal Packing Patterns and Energetics. Crystal Growth & Design, v. 20, n. 8, p. 5143-5159, AUG 5 2020. (17/23960-0, 14/50906-9, 15/20882-3, 13/22127-2)

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)

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

NAKAHATA, Douglas Hideki. Complexos metálicos de sulfonamidas: síntese, caracterização e atividades biológicas. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Química Campinas, SP.