Author(s): Teles, Catherine Morais, 1992- ; Ruiz, Ana Lucia Tasca Gois, 1972- ; Cândido, Tuany Zambroti, 1989- ; Carvalho, João Ernesto de, 1954- ; Lima, Carmen Silvia Passos, 1957- ; Abbehausen, Camilla, 1979-
Date: 2019
Persistent ID: https://hdl.handle.net/20.500.12733/1670959
Origin: Oasisbr
Subject(s): Paládio; Atividade antitumoral; Palladium; Antitumor activity; Selectivity; Artigo original
Agradecimentos: We would like to thank Professor Ana Maria Ferreira da Costa for the elemental analysis. This work was financially supported by São Paulo Research Foundation (FAPESP) processes 2016/07729-4, 2017/12719-0 and 2018/13588-0 and National Council for Scientific and Technological Development (CNPq) grant no. 140384/2016-2 and 406444/2018-8 and partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001
Abstract: A series of PdII complexes with bis-(2-pyridylmethyl)glycine as a ligand of formula [PdX(bis-(2-pyridylmethyl)glycine)] where X = Cl, Br, I were prepared and the effect of the halogen nature in the antitumor activity of eight tumorigenic and one non-tumorigenic cell line was evaluated. The chloride derivative was further functionalized with a transferrin receptor binding peptide, generating the first PdII based metallopeptide. Its antitumor activity was also evaluated. However, among all the complexes, the chloride and iodine parent compounds showed the lowest GI50 values in the panel evaluated, and lowest GI50 than cisplatin in several cell lines. In contrast, the bromine derivative showed higher values of GI50 than chloride and iodine (around 30 - 50 µM). The same trend was observed for the bovine serum albumin binding constant with higher values for iodine, chlorine, and bromine in this order. In aqueous solution, the chloride is exchanged by water while the bromine and iodine are not. DNA was evaluated as a target and showed no significative interaction for all the compounds. The results suggest sulfur-rich proteins and not DNA as a target. This report represents the first PdII metallopeptide reported, its evaluation in solution and antitumor activity. This work opens the possibilities for further functionalization of PdII complexes and the importance of the halogen coordination in the design of novel metallodrugs
COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES
FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
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