Autoimmune Skin Diseases and Immune Checkpoint Inhibitors.

Immune system escape is one of the major strategies required for cancer growths. In this scenario, the advent of immune checkpoint inhibitors (ICIs) revolutionized the landscape of treatment options for tumors. Despite their wide use, these agents are associated with a unique spectrum of toxicities known as immune-related adverse events (irAEs). IrAEs are cause of treatment suspension (up to 60% of all causes of treatment interruption) and potentially impact on patients' quality of life. These toxicities are the main limitations on the use of these innovative drugs. IrAEs are peculiar, due to the mechanism of actions of ICIs, and any body organs may be involved (skin, thyroid, colon, lungs, in particular). Thus, the management often requires a multidisciplinary approach. The aim of this manuscript is to review current literature on autoimmune skin diseases described in association with ICIs (i.e., vitiligo, lupus erythematosus, vasculitis, morphea/scleroderma, alopecia areata, bullous pemphigoid, dermatomyositis), in order to provide a comprehensive overview for the physician.

Fisheries management tools to support coastal and marine spatial planning: A case study from the Northern Gulf of California, Mexico.

A management approach was developed that combined spatial and non-spatial tools to inform a Coastal and Marine Spatial Planning Process (CMSP) in the Puerto Peñasco-Puerto Lobos Coastal Corridor, Northern Gulf of California, Sonora, Mexico. Four fisheries management tools were applied with an emphasis on ecosystem level management for eleven small-scale fisheries. Two spatial management tools, using a spatial prioritization approach, were combined with a permit regularization process, a non-spatial quota prioritization, and a tradeoff analysis in a novel way: • Locally Managed Marine Areas were developed, these are spatial areas where individual community fishermen are assigned the rights to harvest and manage specific fisheries within defined geographic areas. • Fishery refuges that incorporate information on fisheries, ecological importance, and connectivity. • A non-spatial quota prioritization process using a framework for the integrated assessment of stocks, encompassing a vulnerability analysis, a sustainability analysis, and a management framework analysis. • A trade-off analysis of the combination of these different management tools, using an Atlantis ecosystem model for the northern Gulf of California, that tested the ecosystem effects of alternative scenarios to assess benefits in support of ecosystem-based management.

2,6-Bis(2,6-diethylphenyliminomethyl)pyridine coordination compounds with cobalt(II), nickel(II), copper(II), and zinc(II): synthesis, spectroscopic characterization, X-ray study and in vitro cytotoxicity.

Coordination compounds with cobalt(II), nickel(II), copper(II) and zinc(II) and the ligand 2,6-bis(2,6-diethylphenyliminomethyl)pyridine (L) were synthesized and fully characterized by IR and UV-Vis-NIR spectroscopy, elemental analysis, magnetic susceptibility and X-ray diffraction for two representative cases. These novel compounds were designed to study their activity as anti-proliferative drugs against different human cancer cell lines. The tridentate ligand forms heptacoordinated compounds from nitrate metallic salts, where the nitrate acts in a chelating form to complete the seven coordination positions. In vitro cell growth inhibition was measured for Co(II), Cu(II) and Zn(II) complexes, as well as for the free ligand. Upon coordination, the IC50 value of the transition-metal compounds is improved compared to the free ligand. The copper(II) and zinc(II) compounds are the most promising candidates for further in vitro and in vivo studies. The activity against colon and prostate cell lines merits further research, in views of the limited therapeutic options for such cancer types.

Síndrome de Ross: una causa infrecuente neurológica de trastorno de la sudoración / Ross syndrome: an infrequent neurological cause of sweating disorders

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Tuning the cytotoxic properties of new ruthenium(III) and ruthenium(II) complexes with a modified bis(arylimino)pyridine Schiff base ligand using bidentate pyridine-based ligands.

Synthesis, spectroscopy, characterization, structures, and cytotoxicity studies of 2,6-bis(2,6-diisopropylphenyliminomethyl)pyridine (LLL) ruthenium compounds are described. The starting compound [RuCl3(LLL)] has been fully characterized using IR spectroscopy, UV-vis spectroscopy, electrospray ionization mass spectrometry, and NMR spectroscopy. In addition, the crystal structure of the ligand LLL has been determined using single-crystal X-ray diffraction. With the ruthenium(III) trichloride compound as starting material, a new family of Ru(II) complexes with a number of neutral and charged bidentate co-ligands have been synthesized and used for characterization and cytotoxicity studies. The synthesis of the corresponding [Ru(II)LLL(LL)Cl](+/0) complexes with co-ligands- LL is 1,10-phenanthroline, 2,2'-bipyridyl, 2-(phenylazo)pyridine, 2-(phenylazo)-3-methylpyridine, 2-(tolylazo)pyridine, or the anionic 2-picolinate-is reported. Analytical, spectroscopic (IR spectroscopy, UV-vis spectroscopy, (1)H NMR spectroscopy, and electrospray ionization mass spectrometry), and structural characterization of the new compounds is described. Crystal structure analyses of two Ru(II) compounds show a slightly distorted octahedral Ru(II) geometry with tridentate LLL coordinated in a planar meridional fashion, and the chelating co-ligand (LL) and a chloride ion complete the octahedron. The co-ligand plays a significant role in modulating the physicochemical and cytotoxic properties of these new ruthenium complexes. The in vitro cytotoxicity of these new Ru(II) complexes (half-maximal inhibitory concentration, IC50, of 0.5-1.5 µM), in comparison with the parent Ru(III) compound (half-maximal inhibitory concentration of 3.9-4.3 µM) is higher for several of the human cancer cell lines tested. The cytotoxic activity of some of the new ruthenium compounds is even higher than that of cisplatin in the same cancer cell lines. The cytotoxicity of these new anticancer compounds is discussed in the light of structure-based activity relationships, and a possible mechanism of action is suggested.

Novel Organotin(IV) Schiff Base Complexes with Histidine Derivatives: Synthesis, Characterization, and Biological Activity.

Five novel tin Schiff base complexes with histidine analogues (derived from the condensation reaction between L-histidine and 3,5-di-tert-butyl-2-hydroxybenzaldehyde) have been synthesized and characterized. Characterization has been completed by IR and high-resolution mass spectroscopy, 1D and 2D solution NMR ((1)H, (13)C and (119)Sn), as well as solid state (119)Sn NMR. The spectroscopic evidence shows two types of structures: a trigonal bipyramidal stereochemistry with the tin atom coordinated to five donating atoms (two oxygen atoms, one nitrogen atom, and two carbon atoms belonging to the alkyl moieties), where one molecule of ligand is coordinated in a three dentate fashion. The second structure is spectroscopically described as a tetrahedral tin complex with four donating atoms (one oxygen atom coordinated to the metal and three carbon atoms belonging to the alkyl or aryl substituents), with one molecule of ligand attached. The antimicrobial activity of the tin compounds has been tested against the growth of bacteria in vitro to assess their bactericidal properties. While pentacoordinated compounds 1, 2, and 3 are described as moderate effective to noneffective drugs against both Gram-positive and Gram-negative bacteria, tetracoordinated tin(IV) compounds 4 and 5 are considered as moderate effective and most effective compounds, respectively, against the methicillin-resistant Staphylococcus aureus strains (Gram-positive).

Synthesis, single-crystal and solution structure analysis and in vitro cytotoxic activity of two novel complexes of ruthenium(II) with in situ formed flavanone-based ligands.

Synthesis, structure and properties of two new flavanone complexes of Ru(ii) are described. The new complexes form during the reaction of ruthenium(iii) chloride with 3-aminoflavone (3-af) dissolved in an aliphatic alcohol. The formed products depend on the alcohol used and were found to be: cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(ii)·3H(2)O (1) from a methanolic solution and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(ii)·2H(2)O (2) from an ethanolic solution, in which the original ligand 3-af had been converted by dehydrogenative alcoholysis to an entirely new ligand. This paper presents the X-ray structure and detailed (1)H-NMR analysis of both new compounds, as well as the study of their antiproliferative activity. The coordination of Ru(ii) is octahedral with [RuCl(2)N(2)O(2)] chromophores, having trans chlorides and common Ru-L distances. Both 1 and 2 are highly cytotoxic towards the cisplatin resistant EJ and L1210 cell lines, and both complexes are as active as cisplatin in the sensitive cell lines. They display the ability to overcome cisplatin resistance in the drug resistant sub-lines EJcisR and L1210R. The present evidence suggests that the mechanism of biological activity may be different for these ruthenium compounds compared to cisplatin.

Ruthenium(III) chloride complex with a tridentate bis(arylimino)pyridine ligand: synthesis, spectra, X-ray structure, 9-ethylguanine binding pattern, and in vitro cytotoxicity.

The synthetic, spectroscopic, structural, and biological studies of a bis(arylimino)pyridine Ru(III) chloride compound containing the ligand, 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine are reported. The bis(arylimino)pyridine ligand, with three donor nitrogen atoms, was synthesized by condensation of 2,6-pyridinedicarboxaldehyde with 2,4,6-trimethylaniline. The Ru(III) complex, with formula [RuCl 3(L1)](H 2O) (RuL1), where L1 = 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine, was structurally determined on the basis of analytical and spectroscopic (IR, UV-vis, ESI-MS) studies. A straightforward strategy to fully characterize the paramagnetic compound using advanced (1)H NMR is reported. This new complex is a prototype for a series of new anticancer Ru(III) and Ru(II) compounds with improved cytostatic properties; likely to be modified in a desirable manner due to the relatively facile ligand modification of the bis(imino)pyridines and their molecular architecture. The present Ru(III) complex is the first example of this family of Ru(III)/Ru(II) anticancer compounds with the aimed physicochemical characteristics. Although the ligand itself is moderately active in selected cell lines (EVSA-T and MCF-7), the activity of the [Ru(L1)Cl 3] complex has increased significantly for a broad range of cancer cell lines tested in vitro (IC 50 values = 11 approximately 17 microM). Reaction of the RuL1 species with the DNA model base 9-ethylguanine (9EtGua) was found to produce in a redox reaction the species trans-[Ru(II)(L1)(9EtGua) 2(H 2O)](ClO 4) 2 (abbreviated as RuL1-9EtGua), which was studied in solution and also in the solid state, by X-ray crystallography. The structure comprises the as yet unknown trans-bis(purine)Ru(II) unit.

The synthesis, chemical and biological properties of dichlorido(azpy)gold(III) chloride (azpy=2-(phenylazo)pyridine) and the gold-induced conversion of the azpy ligand to the chloride of the novel tricyclic pyrido[2,1-c][1,2,4]benzotriazin-11-ium cation.

A new Au(III) coordination compound with the ligand 2-(phenylazo)pyridine has been synthesized and fully characterized by means of elemental analysis, IR, UV-visible, conductivity measurements, NMR, electrospray ionization (ESI-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). The chemical stability of the cation in this compound, [Au(azpy)Cl(2)](+) (abbreviated: Au-azpy), was analyzed by means of several physicochemical methods. While stable in the solid state, stability studies performed with the gold compound in solution showed an unexpected and unprecedented reactivity. A cationic organic derivative of 2-(phenylazo)pyridine, (abbreviated: pyrium), was produced from the solution and has been isolated as its chloride salt and characterized by crystal structure determination, elemental analysis, NMR, ESI-MS and conductivity studies in solution. This cyclization reaction is reported for the first time in the case of gold coordination compounds. The Au adduct and the pyrium cation were investigated as potential cytotoxic and anticancer agents, and both show moderate to high cytotoxic properties in cisplatin-sensitive and cisplatin-resistant ovarian carcinoma cell lines, A2780; and cisplatin-sensitive and cisplatin-resistant murine lymphocytic leukemia cell lines, L1210. Significant anticancer activity against the cisplatin resistant cell lines was found for the pyrium salt, ruling out the occurrence of cross resistance phenomena.

Interference of ruthenium red analogues at photosystem II of spinach thylakoids.

The effect of ruthenium red analogues on several thylakoid photosynthetic activities has been investigated. RR, RV, RRPh1, RRPh2 and Ph inhibit ATP synthesis and electron flow from water to MV (basal, phosphorylating and uncoupled) as their concentration increases, thus, they act as a Hill reaction inhibitor. They inhibit uncoupled electron transport through PSII from water to DCPIP and partially from DPC to DCPIP. However, these compounds do not affect uncoupled PSI electron transport from DCPIP to MV. Therefore, the target of interaction is at the level of OEC and the span P(680) to Q(A) for RR, RRPh1 and RRPh2. Chlorophyll a fluorescence studies corroborate the already found interference sites and may affect the disconnection between chlorophyll molecules within the LHCII and/or between antennae and RCs, or decreases the exciton to reach the RC and inhibition of PSII occurs. RRPh2 is six times more active than RR. Finally, Ph inhibits electron flow interacting at the level of Q(B).