A 'scorpionate' type precursor [bdtbpza=bis(3,5-di-t-butylpyrazol-1-yl)acetate] has been employed to synthesize two mononuclear Zn(II) and Co(II) derivatives, namely [Zn(bdtbpza)2 (H2O)2].2.5CH3OH.2[(CH3)3C-C3H2N2-C(CH3)3] (1) and [Co(bdtbpza)2(CH3OH)4] (2) in good yield. Single crystal X-ray diffraction analysis reveals that in 1, the Zn(II) atom is tetrahedrally surrounded by a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units and two water molecules; while in 2, the Co(II) atom shows an octahedral environment coordinating a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units along with four methanol molecules. The EPR spectra of 2 recorded at 77 and 298K confirmed the tetragonal symmetry of the high spin Co(II). The DFT (Density functional theory) computation is in good agreement with the geometry proposed for compounds 1 and 2. Both the compounds display a high antiproliferative activity against HCT116 (colorectal carcinoma) and A2780 (ovarian carcinoma) cell lines compared to human normal dermal fibroblasts. In the case of A2780 cells, compounds 1 and 2 exhibit IC50 values that are similar to those described for cisplatin, a widely used chemotherapeutic drug. Exposure of A2780 cells to the IC50 concentration of each compound led to an increase of the number of apoptotic and autophagic cells. In the case of compound 1, the accumulation of intracellular ROS (Reactive oxygen species) is responsible for triggering A2780 cell death.

Herein we report the synthesis of novel ionic liquids (ILs) and organic salts by combining ibuprofen as anion with ammonium, imidazolium, or pyridinium cations. The methodology consists of an acid-base reaction of neutral ibuprofen with cation hydroxides, which were previously prepared by anion exchange from the corresponding halide salts with Amberlyst A-26(OH). In comparison with the parent drug, these organic salts display higher solubility in water and biological fluids and a smaller degree of polymorphism, which in some cases was completely eliminated. With the exception of [C16 Pyr][Ibu] and [N1,1,2,2OH1 ][Ibu], the prepared salts did not affect the viability of normal human dermal fibroblasts or ovarian carcinoma (A2780) cells. Therefore, these ibuprofen-based ionic liquids may be very promising lead candidates for the development of effective formulations of this drug.

While screening for polyhydroxyalkanoate (PHA) producing strains, using glycerol rich by-product as carbon source, it was observed that extracellular polymers were also secreted into the culture broth. The scope of this study was to characterize both intracellular and extracellular polymers, produced by Pseudomonas putida NRRL B-14875 and Pseudomonas chlororaphis DSM 50083, mostly focusing on those novel extracellular polymers. It was found that they fall into the class of bioemulsifiers (BE), as they showed excellent emulsion stability against different hydrocarbons/oils at various pH conditions, temperature and salinity concentrations. Cytotoxicity tests revealed that BE produced by P. chlororaphis inhibited the growth of highly pigmented human melanoma cells (MNT-1) by 50% at concentrations between 150 and 200mug/mL, while no effect was observed on normal skin primary keratinocytes and melanocytes. This is the first study reporting mcl-PHA production by P. putida NRRL B-14785 and bioemulsifier production from both P. putida and P. chlororaphis strains.

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability.

Two mononuclear NiII and MnII compounds, [Ni(bdtbpza)2(CH3OH)4] (1) and [Mn(bdtbpza)2(CH3OH)2(H2O)2] (2), are afforded by employing a ‘scorpionate’ type precursor [bdtbpza = bis(3,5-di-t-butylpyrazol-1-yl)acetate]. The single crystal X-ray structure reveals that the central metal ion (NiII for 1 and MnII for 2) is surrounded by a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units, while four OMeOH donors for 1 and two OMeOH plus two Owater for 2 complete the first coordination sphere. Thus, both compounds exhibit a slightly distorted octahedral geometry possessing an O6 coordination environment. EPR spectra of CuII-doped 1 and of 2 recorded on the polycrystalline solids and in organic solution confirm the octahedral geometry around the metal ions and the binding of six oxygen atoms. The electrochemical study of compounds 1 and 2 shows that one electron reduction of MnII occurs at a more negative potential than NiII, indicating a lower tendency of reduction for Mn than Ni. Both compounds displayed a high cytotoxic activity against A2780 ovarian carcinoma cells and no cytotoxic activity in normal primary human fibroblasts for concentrations up to 55 μM. Notwithstanding, compound 1 is found to be the most cytotoxic towards A2780 cancer cells. The cytotoxic activity of compound 1 is correlated with the induction of apoptosis associated with a higher mitochondria dysfunction and autophagy cell death. In addition, the compounds can induce oxidative damage leading to ROS accumulation. Overall, the data presented here demonstrate that 1 has potential for further in vivo studies aiming at its future application in ovarian cancer therapy.

Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(IV) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(IV) complex with an aromatic oximehydroxamic acid group [nBu2Sn(L)]3(H2L = N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) – MG85 – and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts.

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4′-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.