ABSTRACT
Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 +/- 3.23) microM and (137.65 +/- 0.22) microM for 1 and (39.7 +/- 0.30) microM and (146.51 +/- 2.67) microM for 2, respectively. The production of NO, IL-12, and TNF-alpha, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Palladium/pharmacology , Animals , Cell Line, Tumor , Mice , Nitric Oxide/metabolismABSTRACT
Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The antimycobacterial activity and the innate immune response of methanol (METH) and dichloromethane (DCM) extracts of Indigofera suffruticosa Miller (Fabaceae) were evaluated. We observed that the minimum inhibitory concentrations (MICs) for METH and DCM extracts were 125 and 1000 microg/mL, respectively. However, they were able to induce the innate immune response through the production of high levels of NO and TNF-alpha (p < 0.001) by peritoneal exudate cells (PECs). These results suggest that I. suffruticosa extracts may have an important immunological role in the control of TB once macrophage activity is induced by them.
Subject(s)
Anti-Bacterial Agents/pharmacology , Immunity, Innate/drug effects , Indigofera , Mycobacterium tuberculosis/drug effects , Plant Extracts/pharmacology , Animals , Anti-Bacterial Agents/isolation & purification , Cell Survival/drug effects , Cell Survival/immunology , Cells, Cultured , Immunity, Innate/immunology , Mice , Microbial Sensitivity Tests/methods , Mycobacterium tuberculosis/immunology , Plant Components, Aerial , Plant Extracts/isolation & purificationABSTRACT
The activities of perlatolic acid (1), atranorin (2), and lecanoric acid (3) and their derivatives, such as orsellinates and beta-methyl orsellinates obtained by alcoholysis, were assessed for stimulation of the release of hydrogen peroxide and nitric oxide in cultures of peritoneal macrophage cells from mice. The hydrogen peroxide production was estimated by oxidation of phenol red, while the Griess reagent was used to determine the nitric oxide production. 1 and 4-methoxy-ethyl orsellinate (XVII) were the compounds that induced the greatest release of H2O2, whereas n-pentyl orsellinate (IV), iso-propyl orsellinate (V), sec-butyl orsellinate (VI), and XVII induced a small release of NO. These results indicate that lichen products and their derivatives have potential immune-modulating activities.
Subject(s)
Hydrogen Peroxide/metabolism , Lichens/metabolism , Macrophages/metabolism , Nitric Oxide/metabolism , Plant Extracts/metabolism , Animals , MiceABSTRACT
The reactions between [Pd(C(2),N-dmba)(micro-X)](2) (dmba=N,N-dimethylbenzylamine; X=Cl, Br) and thiourea (tu) in the 1:2 molar ratio at room temperature resulted in the mononuclear compounds [Pd(C(2),N-dmba)(Cl)(tu)] (1) and [Pd(C(2),N-dmba)(Br)(tu)] (2), which were characterized by elemental analyses and infrared (IR), (1)H- and (13)C{(1)H} NMR spectroscopies. The crystal and molecular structures of 2 were determined by single-crystal X-ray diffraction. In vitro cytotoxicity assays of the compounds 1, 2, tu, dmba and cisplatin were carried out using two murine tumor cell lines, namely mammary adenocarcinoma (LM3) and lung adenocarcinoma (LP07). The compounds 1, 2, tu and dmba were also tested against Mycobacterium tuberculosis and their MIC values were determined.
