Citotoxicity and immune response induced by organopalladium(II) compounds in mice bearing Ehrlich ascites tumour

Abstract

Os ciclometalados de paládio(II) são compostos inorgânicos reativos empregados em vários estudos biológicos devido a seu potencial antitumoral e interação com o sistema imune. Neste estudo, a resposta imune e citotóxica induzida por dois complexos organopaladados: [{Pd(N,C-dmba)} 2 (μ-NCS) 2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'-dimetilbenzilamina, dppp = 1,3-bis(difenilfosfino)propano] e cisplatina (cis-DDP), como padrão, foram investigados em camundongos portadores do tumor ascítico de Ehrlich. Os camundongos foram divididos em cinco grupos e inoculados com (1) ou (2) ou cis-DDP ou apenas veículo ou solução salina tamponada de fosfatos (PBS). Diversos parâmetros foram avaliados, tais como a porcentagem de células tumorais presentes no exsudato peritoneal, os níveis de óxido nítrico (NO) e fator de necrose tumoral (TNF-α) séricos e o aumento na expectativa de vida. Os dados obtidos demonstram que o composto (2) apresentou atividade similar à da cis-DDP, como, por exemplo, aumento na expectativa de vida, diminuição dos níveis séricos de TNF-α e aumento da produção de NO.Cyclometallated palladium(II) complexes are reactive inorganic compounds employed in several biological studies because of their antitumour potential and interaction with immune system. In the present study, the immune and citotoxic response induced by two organopalladated complexes: [{Pd(N,C-dmba)} 2 (μ-NCS) 2 ] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N'-dimethylbenzylamine, dppp = 1,3-bis(diphenylphosphino)propane] and cisplatin (cis-DDP), as standard, were investigated in mice bearing Ehrlich ascites tumour. The mice were divided into five groups and inoculated with the compounds (1) or (2) or cisplatin, or only vehicle or phosphatebuffered saline (PBS). Many parameters were evaluated, such as tumour cell percentage in the peritoneal exsudate, levels of seric nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and increase in life span. Analysis of all data revealed, for compound (2), an activity similar to that presented by cisplatin, resulting in increased life span, lower levels of seric TNF-α and increase in NO production.Keywords: palladium(II) complexes, Ehrlich ascites tumour, macrophages, nitric oxide, tumour necrosis factor-alpha. IntroductionCancer is a disease in which unremitting clonal expansion of somatic cells kills by invading, subverting, and eroding normal tissues. 1 Millions of people die every year from the metastatic spread of cancer that occurs through blood and lymphatic vessels or directly into tissues and body cavities. 2 Between the several types of cancer, breast cancer is the most common malignancy in women worldwide. 3 In some cases, immune cells constitute a prominent component of the host response to cancer, but their participation in tumour pathogenesis remains not completely understood. Dense intratumoral lymphocyte cis-Diamminedichloroplatinum(II), 9 a clinically important antitumour drug, acts like a classical alkylating agent in chemotherapy against some types of cancers. It is a potent ...

Antitumor and antimycobacterial activities of cyclopalladated complexes: X-ray structure of [Pd(C2,N-dmba)(Br)(tu)] (dmba =N,N-dimethylbenzylamine, tu = thiourea)

“…Cis-Diamminedichloroplatinum (II) is a clinically important antitumor drug [1,2] which reacts with nucleophilic sites in DNA forming monoadducts as well as intra-and interstrand cross-links, but its administration in humans shows many side-effects such as nausea, nephrotoxicity and neurotoxicity [3,4]. Due to these adverse effects, research moved on to second and third-generation platinum compounds like carboplatin [1] and oxaliplatin [4], respectively, as well as to other metal complexes with improved pharmacological properties [5,6].…”

“…To overcome this high lability, chelating ligands have been used to yield high thermodynamically stable and kinetically inert Pd(II) complexes [4]. Within this context, the tertiary amine N,N-dimethylbenzylamine (dmba) represents a good choice to prepare new ortho-cyclopalladated complexes with promising in vivo and in vitro cytotoxicity [3,4]. For instance, the compound [Pd 2 (C 2 ,N-S (À) dmpa) 2 (m-dppf)(Cl) 2 ] (dmpa ¼ N,N-dimethyl-1-phenethylamine; dppf ¼ 1,1 0 -bis(diphenylphosphine)ferrocene) has shown antimetastatic effects [8].…”

Immunomodulatory effects of palladium(II) complexes of 1,2,4-triazole on murine peritoneal macrophages

“…As ligands, 1,2,4-triazoles are extremely versatile and display the ability to act as monodentate, exobidentate N(1),N (2) and exobidentate N (2),N(4) when neutral or monodentate, exobidentate N (1),N (2), exobidentate N (1), N(4) and N (1),N (2),N(4)-tridentate when deprotonated. 17 In pursuing our interest on chemical and biological aspects of palladium(II) complexes, 14,18,19 we describe in this work the synthesis, spectroscopic characterization and thermal investigation of the two new 1,2,4-triazolylbridged polynuclear complexes [{PdCl 2 (µ-Htrz)} n ] (1) and [{PdBr 2 (µ-Htrz)} n ] (2). We also investigated the immunomodulatory effects of the compounds 1,2,4-triazole (Htrz), 1, 2, and cisplatin by the release of NO and H 2 O 2 in the culture supernatants of treated murine peritoneal cells.…”

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

“…Based on the potential activity of the cyclopalladated complexes reported in the literature, [28][29][30][31][32][33][34] in this study, we describe the evaluation of the leishmanicidal and trypanocidal activity of [Pd(dmba) (Figure 1), dmba: N,N'-dimethylbenzylamine and isn: isonicotinamide. All complexes have been previously described [35][36][37][38] but their protozoal activities have not been reported yet.…”

“…Based on the potential activity of the cyclopalladated complexes reported in the literature, [28][29][30][31][32][33][34] The elemental analysis was performed with an Elemental Analyzer 2400 CHN, PerkinElmer, at Central Analítica, Instituto de Química, USP, São Paulo, Brazil.…”