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

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 (5)
(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; TROVATTI, ELIANE; LUSTRI, WILTON ROGERIO; RESENDE, FLAVIA AP. Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential. Planta Medica, JAN 2021. Web of Science Citations: 0.
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.; LUSTRI, BRUNA C.; MACHADO RIBEIRO, TAMARA RENATA; MOREIRA, CRISTIANO G.; CANDIDO, TUANY ZAMBROTI; PASSOS LIMA, CARMEN SILVIA; RUIZ, ANA LUCIA T. G.; CORBI, PEDRO P.; LUSTRI, WILTON R. 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. Web of Science Citations: 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. Web of Science Citations: 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. Web of Science Citations: 0.
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. Web of Science Citations: 1.

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