Macrophage Activity under Hyperglycemia: A Study of the Effect of Resveratrol and 3H-1,2-Dithiole-3-thione on Potential Polarization.

Currently, research is focused on bioactive compounds with the potential to promote macrophage polarization with the aim of reducing the development of inflammatory-related diseases. However, the effect of bioactive compounds under oxidative-stress-induced hyperglycemia on macrophage polarization has been scarcely investigated. RAW 264.7 macrophages were incubated under standard (SG) or high glucose (HG) conditions and stimulated with lipopolysaccharide (LPS) (10, 60 and 100 ng/mL) to monitor macrophage polarization after resveratrol (RSV) or 3H-1,2-dithiole-3-thione (D3T) supplementation (2.5, 5, 10 and 20 µM). Under SG and HG conditions without LPS stimulation, RSV significantly decreased macrophage viability at the highest concentration (20 µM), whereas D3T had no or low effect. LPS stimulation at 60 and 100 ng/mL, under SG and HG conditions, increased significantly macrophage viability. Both RSV and D3T significantly decreased NO production in LPS-stimulated macrophages under HG condition, whereas only D3T increased GSH levels at 100 ng/mL and normalized MDA values at 60 ng/mL of LPS under HG condition. Under 60 ng/mL LPS stimulation and HG, mRNA IL-1 and IL-6 were higher. Interestingly, RSV decreased pro-inflammatory interleukins; meanwhile, D3T increased Arg1 and IL-10 relative expression. Overall, our results indicate that hyperglycemia plays a fundamental role in the modulation of macrophage-induced inflammation in response to bioactive compounds.

4,5-Diferrocenyl-1,2-di-thiole-3-thione.

The structure of 4,5-diferrocenyl-1,2-di-thiole-3-thione, [Fe2(C5H5)2(C13H8S3)] or C23H18Fe2S3, at 130 K has monoclinic (P21/c) symmetry. The molecule has two ferrocenyl units attached to a 1,2-di-thiole-3-thione moiety. It is of inter-est with respect to the question if the introduction of ferrocenyl substituents into biologically active mol-ecules offers the potential to obtain more efficacious therapeutic drugs. The crystal structure displays inter-molecular contacts of the C-H⋯S and S-π(C-C) types.

Role of sulforaphane in endoplasmic reticulum homeostasis through regulation of the antioxidant response.

Nowadays, the nutraceutical agent sulforaphane (SFN) shows great versatility in turning on different cellular responses. Mainly, this isothiocyanate acts as a master regulator of cellular homeostasis due to its antioxidant response and cytoplasmic, mitochondrial, and endoplasmic reticulum (ER) protein modulation. Even more, SFN acts as an effective strategy to counteract oxidative stress, apoptosis, and ER stress, among others as seen in different injury models. Particularly, ER stress is buffered by the unfolded protein response (UPR) activation, which is the first instance in orchestrating the recovery of ER function. Interestingly, different studies highlight a close interrelationship between ER stress and oxidative stress, two events driven by the accumulation of reactive oxygen species (ROS). This response inevitably perpetuates itself and acts as a vicious cycle that triggers the development of different pathologies, such as cardiovascular diseases, neurodegenerative diseases, and others. Accordingly, it is vital to target ER stress and oxidative stress to increase the effectiveness of clinical therapies used to treat these diseases. Therefore, our study is focused on the role of SFN in preserving cellular homeostasis balance by regulating the ER stress response through the Nrf2-modulated antioxidant pathway.

One- and two-dimensional PbII compounds resulting from reaction of PbBr2 and Pb(SCN)2 with pyrimidine-2-thione.

Pyrimidine-2-thione (HSpym) reacts with lead(II) thiocyanate and lead(II) bromide in N,N-dimethylformamide (DMF) to form poly[(µ-isothiocyanato-κ2N:S)(µ4-pyrimidine-2-thiolato-κ6N1,S:S:S:S,N3)lead(II)], [Pb(C4H3N2S)(NCS)]n or [Pb(Spym)(NCS)]n, (I), and the polymeric one-dimensional (1D) compound catena-poly[[µ4-bromido-di-µ-bromido-(µ-pyrimidine-2-thiolato-κ3N1,S:S)(µ-pyrimidine-2-thione-κ3N1,S:S)dilead(II)] N,N-dimethylformamide monosolvate], {[Pb2Br3(C4H3N2S)(C4H4N2S)]·C3H7NO}n or {[Pb2Br3(Spym)(HSpym)]·DMF}n, (IIa), respectively. Poly[µ4-bromido-di-µ3-bromido-(µ-pyrimidine-2-thiolato-κ3N1,S:S)(µ-pyrimidine-2-thione-κ3N1,S:S)dilead(II)], [Pb2Br3(C4H3N2S)(C4H4N2S)]n or [Pb2Br3(Spym)(HSpym)]n, (IIb), could be obtained as a mixture with (IIa) when using a lesser amount of solvent. In the crystal structures of the pseudohalide/halide PbII stable compounds, coordination of anionic and neutral HSpym has been observed. Both Spym- (in the thiolate tautomeric form) and NCS- ligands were responsible for the two-dimensional (2D) arrangement in (I). The Br- ligands establish the 1D polymeric arrangement in (IIa). Eight-coordinated metal centres have been observed in both compounds, when considering the Pb...S and Pb...Br interactions. Both compounds were characterized by FT-IR and diffuse reflectance spectroscopies, as well as by powder X-ray diffraction. Compound (IIa) and its desolvated version (IIb) represent the first structurally characterized PbII compounds containing neutral HSpym and anionic Spym- ligands. After a prolonged time in solution, (IIa) is converted to another compound due to complete deprotonation of HSpym. The structural characterization of (I) and (II) suggests HSpym as a good candidate for the removal of PbII ions from solutions containing thiocyanate or bromide ions.

Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents.

The current anticancer and antileishmanial drug arsenal presents several limitations concerning their specificity, efficacy, costs and the emergence of drug-resistant cells lines, which encourages the urgent need to search for new alternatives. Inspired by the fact that gold(I)-based compounds are promising antitumoral and antileishmanial drug candidates, we synthesized novel gold(I) complexes containing phosphine and 5-phenyl-1,3,4-oxadiazole-2-thione and evaluated their anticancer and antileishmanial activities. Synthesis was performed by reacting 5-phenyl-1,3,4-oxadiazole-2-thione derivatives with chloro(triphenylphosphine)gold(I) and chloro(triethylphosphine)gold(I). The novel compounds were characterized by infrared, Raman, 1H, 13C nuclear magnetic resonance, high-resolution mass spectra, and x-ray crystallography. The coordination of the ligands to gold(I) occurred through the exocyclic sulfur atom. All gold(I) complexes were active at low micromolar or nanomolar range with IC50 values ranging from <0.10 to 1.66 µM against cancer cell lines and from 0.9 to 4.2 µM for Leishmania infantum intracellular amastigotes. Compound (6-A) was very selective against murine melanoma B16F10, colon cancer CT26.WT cell lines and L. infantum intracellular amastigotes. Compound (7-B) presented the highest anticancer activity against both cancer cell lines while the promising antileishmanial lead was compound (6-A). Tiethylphosphine gold(I) complexes were more active than the conterparts triphenylphosphine derivatives for both anticancer and antileishmanial activities. Triethylphosphine gold(I) derivatives presented antimony cross-resistance in L. guyanensis demonstrating their potential to be used as chemical tools to better understand mechanisms of drug resistance and action. These findings revealed the anticancer and antileishmanial potential of gold(I) oxadiazole phosphine derivatives.

Crystal structures of two chiral piperidine derivatives: 1-[(1R)-2-hy-droxy-1-phenyl-eth-yl]piperidin-4-one and 8-[(1S)-1-phenyl-eth-yl]-1,4-dioxa-8-aza-spiro-[4.5]decane-7-thione.

The crystal structures of the two title piperidine derivatives show different conformations for the six-membered heterocycle. The N-substituted 4-piperidinone 1-[(1R)-2-hy-droxy-1-phenyl-eth-yl]piperidin-4-one, C13H17NO2, (I), has a chair conformation, while the piperidine substituted in position 2 with a thio-carbonyl group, 8-[(1S)-1-phenyl-eth-yl]-1,4-dioxa-8-aza-spiro-[4.5]decane-7-thione, C15H19NO2S, (II), features a half-chair conformation. Comparison of the two structures, and data retrieved from the literature, suggests that the conformational flexibility is mainly related to the hybridization state of the C atom α to the piperidinic N atom: a Csp (3) atom favours the chair conformer, while a Csp (2) atom distorts the ring towards a half-chair conformer. In the crystal structure of (I), weak C-H⋯O hydrogen bonds link the mol-ecules into supra-molecular chains propagating along the b-axis direction. In the crystal of (II), the mol-ecules are linked by weak C-H⋯S contacts into supra-molecular chains propagating along the b-axis direction.

Aminosilanes derived from 1H-benzimidazole-2(3H)-thione.

Two new molecular structures, namely 1,3-bis(trimethylsilyl)-1H-benzimidazole-2(3H)-thione, C13H22N2SSi2, (2), and 1-trimethylsilyl-1H-benzimidazole-2(3H)-thione, C10H14N2SSi, (3), are reported. Both systems were derived from 1H-benzimidazole-2(3H)-thione. Noncovalent C-H···π interactions between the centroid of the benzmidazole system and the SiMe3 groups form helicoidal arrangements in (2). Dimerization of (3) results in the formation of R2(2)(8) rings via N-H···S interactions, along with parallel π-π interactions between imidazole and benzene rings.