Synthesis of metal complexes with bioactive N,N or N,O-coordinating ligands for use in sustainable delivery system based on bacterial cellulose

• Grant number: 18/12590-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2018
• End date: March 31, 2021
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Wilton Rogério Lustri
• Grantee: Wilton Rogério Lustri
• Host Institution: Universidade de Araraquara (UNIARA). Associação São Bento de Ensino. Araraquara , SP, Brazil
• Associated researchers: Andréia Bagliotti Meneguin ; Hernane da Silva Barud ; Pedro Paulo Corbi
• Associated research grant(s): 19/23493-9 - Development of bacterial cellulose/MOF composite for sustained package, AP.R SPRINT

Abstract

Metallic complexes have been used since ancient times in medicine to treat various diseases. As an example, Au (I) complexes, such as auranofin, used clinically in the treatment of rheumatoid arthritis, Ag (I) complexes, which have antimicrobial properties, such as silver sulfadiazine, topically used in severe burns for the prevention of bacterial infections as well as the platinum metal complexes, such as cisplatin, carboplatin, oxaliplatin, nedaplatin and lobaplatin used in the treatment of cancer. In the case of cancer, chemotherapy represents the backbone of treatment for many types of tumors at different stages of evolution, although in many cases resistance to chemotherapy may occur, which may determine the therapeutic failure and, generally, the death of the tumor. patient. In addition to cancer, the indiscriminate use of antibacterial agents has provided the selection of resistant and increasingly virulent species of pathogenic bacteria, associated with human infections, which brings serious difficulties to the effectiveness of the treatment with the antimicrobials used in the clinic. Thus, development of coordination compounds with antitumor, antimicrobial, efficacy and safety, and interactions with biomolecules can revolutionize the therapeutic arsenal for the treatment of these diseases, especially in the case of resistance. Currently, the use of biopolymers as support and release of drugs has gained great importance in medicine. Among these polymers, bacterial cellulose (CB) is a great promise in biomedical applications because of its combination of biocompatibility and great versatility. CB, in different forms, has already been applied in the treatment of various types of injuries such as barriers and supports in the regeneration of periodontal tissues, temporary artificial skin for burns and ulcers and artificial blood vessels for microsurgery and support for drug release. The objective of this research project is to synthesize metallic complexes of copper (II), silver (I), gold (III), zinc (II), Mg (II), palladium (II), platinum bioactive binders 4-aminobenzoic acid (pABA), allopurinol, 1-hydroxybenzotriazole (HoBt) and probenecid for applications as antimicrobial agents for topical use and as antitumor, as well as incorporate the metal complexes into polymeric and nanostructured carriers. The present project also aims to produce pure CB membranes using the genus G. hansenii ATCC 23769 original, G. hansenii ATCC 23769 genetically modified and hybrid membrane production, from co-cultures with the other biopolymer producing species as P. aeruginosa (ATCC 27853) and Capriavidus necator ATCC17699, in order to obtain membranes with special fiber interlacing characteristics for use as support for sustained release of the free and incorporated metal complexes incorporated into the polymer carriers. (AU)

Scientific publications

(11)

(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)

MARENA, GABRIEL DAVI; GIROTTO, LUIZA; SALDANHA, LUIZ LEONARDO; RAMOS, MATHEUS APARECIDO DOS SANTOS; DE GRANDIS, RONE APARECIDO; DA SILVA, PATRICIA BENTO; DOKKEDAL, ANNE LIGIA; CHORILLI, MARLUS; BAUAB, TAIS MARIA; PAVAN, FERNANDO ROGERIO; et al. Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential. Planta Medica, JAN 2021. (16/08559-5, 17/16278-9, 18/12590-0, 17/18782-6)

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., 2022-09-01. (21/08717-8, 13/07937-8, 18/12590-0, 17/25995-6, 15/25114-4, 18/12062-4)

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)

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)

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)

MARENA, GABRIEL DAVI; GIROTTO, LUIZA; SALDANHA, LUIZ LEONARDO; RAMOS, MATHEUS APARECIDO DOS SANTOS; DE GRANDIS, RONE APARECIDO; DA SILVA, PATRICIA BENTO; DOKKEDAL, ANNE LIGIA; CHORILLI, MARLUS; BAUAB, TAIS MARIA; PAVAN, FERNANDO ROGERIO; et al. Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential. Planta Medica, v. 88, n. 05, p. 11-pg., 2021-01-28. (17/18782-6, 17/16278-9, 18/12590-0, 16/08559-5)

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)

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)

CANDIDO, TUANY ZAMBROTI; FERRAZ DE PAIVA, RAPHAEL ENOQUE; FIGUEIREDO, MARIANA CECCHETTO; COSER, LILIAN DE OLIVEIRA; LAZARINI FRAJACOMO, SILMARA CRISTINA; ABBEHAUSEN, CAMILLA; CARDINALLI, IZILDA APARECIDA; LUSTRI, WILTON ROGERIO; CARVALHO, JOAO ERNESTO; TASCA GOIS RUIZ, ANA LUCIA; et al. Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma. PHARMACEUTICS, v. 14, n. 2, p. 18-pg., 2022-02-01. (16/07729-4, 18/12062-4, 15/09833-0, 17/12719-0, 18/12590-0)

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)