New Palladium(II) Complexes Containing Methyl Gallate and Octyl Gallate: Effect against Mycobacterium tuberculosis and Campylobacter jejuni.

This work describes the preparation, characterization and antimicrobial activity of four palladium(II) complexes, namely, [Pd(meg)(1,10-phen)] 1, [Pd(meg)(PPh3)2] 2, [Pd(og)(1,10-phen)] 3 and [Pd(og)(PPh3)2] 4, where meg = methyl gallate, og = octyl gallate, 1,10-phen = 1,10-phenanthroline and PPh3 = triphenylphosphine. As to the chemical structures, spectral and physicochemical studies of 1-4 indicated that methyl or octyl gallate coordinates a palladium(II) ion through two oxygen atoms upon deprotonation. A chelating bidentate phenanthroline or two triphenylphosphine molecules complete the coordination sphere of palladium(II) ion, depending on the complex. The metal complexes were tested against the Mycobacterium tuberculosis H37Rv strain and 2 exhibited high activity (MIC = 3.28 µg/mL). As to the tests with Campylobacter jejuni, complex 1 showed a significant effect in reducing bacterial population (greater than 7 log CFU) in planktonic forms, as well as in the biomass intensity (IBF: 0.87) when compared to peracetic acid (IBF: 1.11) at a concentration of 400 µg/mL. The effect provided by these complexes has specificity according to the target microorganism and represent a promising alternative for the control of microorganisms of public health importance.

Antimicrobial Resistance Challenged with Platinum(II) and Palladium(II) Complexes Containing 1,10-Phenanthroline and 5-Amino-1,3,4-Thiadiazole-2(3H)-Thione in Campylobacter jejuni.

This work describes the synthesis and characterization of two metal complexes of the type [M(L1)2(phen)], where M = Pt2+ (complex I) or Pd2+ (complex II), L1 = 5-amino-1,3,4-thiadiazole-2(3H)-thiolate and phen = 1,10-phenanthroline. The in vitro antibacterial activity of these complexes was investigated in isolation and synergistically with ciprofloxacin (CIP) and erythromycin (ERY) in three strains of Campylobacter jejuni (MIC = 32 mg/L for CIP and ERY), selected from a bank of 235 strains representative of three poultry exporting states of the country (A, B and C), previously analyzed for epidemiology and resistance to CIP and ERY. A total of 53/235 (22.55%) strains showed co-resistance to CIP and ERY. Isolated resistance to CIP was higher than to ERY. Epidemiological analysis showed that resistance to CIP was more evident in state B (p < 0.0001), as well as a higher susceptibility to ERY in state C (p = 0.0028). Co-resistance was expressive in state A and in the spring and fall seasons. The evaluation of I alone and in synergy with CIP and ERY found values up to 0.25 mg/L not significant for ERY. Complex II did not show an antimicrobial effect on the three strains of tested C. jejuni. The effect provided by complex I represents a promising alternative for control of resistant strains of C. jejuni.

Gold(III) complexes with thiosemicarbazonate ligands as potential anticancer agents: Cytotoxicity and interactions with biomolecular targets.

Gold(III) complexes have been studied for the past years due to their anticancer properties and great affinity to biotargets, such as enzymes and proteins, which support their pharmacological applications. Within this scope, in this work the antiproliferative activities of two Au(III)-thiosemicarbazonate complexes, [AuClL1] (1, L1: (E,Z)-N-ethyl-N'-(3-nitroso-kN)butan-2-ylidene)carbamohydrazonothioato-k2N2,S) and [Au(Hdamp)L2]Cl (2, L2: N-(N'',N''-diethylaminothiocarbonyl)-N'(N''', N'''-dimethylcarbothioamide)benzamidineto-kN,k2S and Hdamp: 2-(N,N-dimethylaminomethyl)-phenyl-C1), and their affinities to possible biological targets were investigated. Three different tumor cell lines were used to perform the cytotoxicity assays, including one cisplatin-resistant model, and the results showed lower EC50 for 1 over 2 in every case: B16F10 (4.1 µM and 15.6 µM), A431 (4.0 µM and >50 µM) and OVCAR3 (4.2 µM and 24.5 µM). However, a lower toxicity to fibroblast 3T3 cell line was observed for 2 (30.58 µM) when compared to 1 (7.17 µM), resulting in comparable therapeutic indexes. Both complexes presented strong affinity to HSA: they distorted the secondary structure of the protein, as verified by circular dichroism, but 1 additionally presented the apparent fluorescence quenching constant (Kapp) ten times greater than 2, which was probably due to the fact of 1 being able to denature HSA. The ethidium bromide displacement assay showed that neither 1 nor 2 are strong DNA intercalators, which is in agreement with what was observed through the UV-vis titration. In both cases, the 260 nm band presented hyperchromism, which can indicate ionic interactions or DNA damage. In fact, 1 was able to damage the pGEM plasmid, similarly to cisplatin, as verified by agarose gel electrophoresis and Atomic Force Microscopy. Biophysical studies in cancer cells model membranes were also performed in order to investigate the interaction of the gold complexes to lipid bilayers and revealed that the compounds interact with the membranes by exhibiting partition coefficients of 103 order of magnitude. Overall, both complexes were found to be promising candidates for the development of a future anticancer drug against low sensitive or cisplatin resistant tumors.