Cyclometalated complexes: promising metallodrugs in the battle against cancer.

Metal-based compounds are excellent alternative drugs for oncological treatment and research. The successful use of cisplatin and its derivatives clearly exemplifies the important role of such compounds in cancer therapy. However, the low selectivity, side effects, and resistance associated with this drug have led to the search for new strategies to overcome these limitations.

Protoporphyrin IX-Derived Ruthenium(II) Complexes for Photodynamic Therapy in Gastric Cancer Cells.

In recent years, photodynamic therapy (PDT) has emerged as a promising alternative to classical chemotherapy for treating cancer. PDT is based on a nontoxic prodrug called photosensitizer (PS) activated by light at the desired location. Upon irradiation, the PS reacts with the oxygen present in the tumor, producing cytotoxic reactive oxygen species (ROS).

Evaluation of the Antifungal Properties of Azomethine-Pyrazole Derivatives from a Structural Perspective.

About 95 % of candidiasis infections worldwide are attributed to five Candida fungi species, with C. albicans being the most prevalent and severe. Due to resistance phenomena, the last decade has seen a significant challenge for candidiasis treatment with antifungal drugs, which has led to an urgent need for new antifungal agents.

The lamprey habenula provides an extreme example for the temporal regulation of asymmetric development.

By their phylogenetic position and their marked epithalamic asymmetries, lampreys are relevant models for understanding the formation and evolution of this trait across vertebrates. In this study, we use a transcriptomic approach to identify novel signature markers to characterize the highly asymmetric, bipartite organization of habenulae in lampreys. Lamprey habenulae are subdivided into two complementary subdomains related, respectively, to the lateral/ventral and the medial/dorsal habenulae of jawed vertebrates: a dorsal, right-restricted subdomain and a bilateral subdomain that includes the left habenula as well as its ventral right counterpart.

The Sensory Shark: High-quality Morphological, Genomic and Transcriptomic Data for the Small-spotted Catshark Scyliorhinus Canicula Reveal the Molecular Bases of Sensory Organ Evolution in Jawed Vertebrates.

Cartilaginous fishes (chondrichthyans: chimeras and elasmobranchs -sharks, skates, and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic, and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterize general aspects of the catshark genome, confirming the high conservation of genome organization across cartilaginous fishes, and investigate population genomic signatures.

Analysis of a shark reveals ancient, Wnt-dependent, habenular asymmetries in vertebrates.

The mode of evolution of left-right asymmetries in the vertebrate habenulae remains largely unknown. Using a transcriptomic approach, we show that in a cartilaginous fish, the catshark Scyliorhinus canicula, habenulae exhibit marked asymmetries, in both their medial and lateral components. Comparisons across vertebrates suggest that those identified in lateral habenulae reflect an ancestral gnathostome trait, partially conserved in lampreys, and independently lost in tetrapods and neopterygians.

Diversification of habenular organization and asymmetries in teleosts: Insights from the Atlantic salmon and European eel.

Habenulae asymmetries are widespread across vertebrates and analyses in zebrafish, the reference model organism for this process, have provided insight into their molecular nature, their mechanisms of formation and their important roles in the integration of environmental and internal cues with a variety of organismal adaptive responses. However, the generality of the characteristics identified in this species remains an open question, even on a relatively short evolutionary scale, in teleosts. To address this question, we have characterized the broad organization of habenulae in the Atlantic salmon and quantified the asymmetries in each of the identified subdomains.

Targeting of the intracellular redox balance by metal complexes towards anticancer therapy.

The development of cancers is often linked to the alteration of essential redox processes, and therefore, oxidoreductases involved in such mechanisms can be considered as attractive molecular targets for the development of new therapeutic strategies. On the other hand, for more than two decades, transition metals derivatives have been leading the research on drugs as alternatives to platinum-based treatments. The success of such compounds is particularly due to their attractive redox kinetics properties, favorable oxidation states, as well as routes of action different to interactions with DNA, in which redox interactions are crucial.

Preparation and Characterization of Strongly Sulfonated Acid Block and Random Copolymer Membranes for Acetic Acid Esterification with 2-Propanol.

In this paper, we report the synthesis of block and random copolymers of 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) and methyl methacrylate (MMA), with different AMPS feed ratios. These solution-processable copolymers with strongly sulfonated acid groups resulted in membranes with tunable ion exchange (IEC) and water absorption capacities. AFM images confirmed the microphase separation of block copolymer membrane, annealed under the appropriate conditions.

Evolutionary Transition in the Regulation of Vertebrate Pronephros Development: A New Role for Retinoic Acid.

The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including genes and retinoic acid (RA), which play well-characterized roles in the organization of the chordate body plan. The intermediate mesoderm (IM), which gives rise to all vertebrate kidneys, is an example of a tissue that differentiates sequentially along this axis. Yet, the conservation of the spatiotemporal regulation of the IM across vertebrates remains poorly understood.

Synthesis, Structural Characterization, and In Vitro and In Silico Antifungal Evaluation of Azo-Azomethine Pyrazoles (PhN(PhOH)CHN(CN(CH))PhR, R = H or NO).

The azo-azomethine imines, R-N=N-R-CH=N-R, are a class of active pharmacological ligands that have been prominent antifungal, antibacterial, and antitumor agents. In this study, four new azo-azomethines, R = Ph, R = phenol, and R = pyrazol-Ph-R' (R = H or NO), have been synthesized, structurally characterized using X-ray, IR, NMR and UV-Vis techniques, and their antifungal activity evaluated against certified strains of and . The antifungal tests revealed a high to moderate inhibitory activity towards both strains, which is regulated as a function of both the presence and the location of the nitro group in the aromatic ring of the series.

When Bigger Is Better: 3D RNA Profiling of the Developing Head in the Catshark .

We report the adaptation of RNA tomography, a technique allowing spatially resolved, genome-wide expression profiling, to a species occupying a key phylogenetic position in gnathostomes, the catshark . We focused analysis on head explants at an embryonic stage, shortly following neural tube closure and of interest for a number of developmental processes, including early brain patterning, placode specification or the establishment of epithalamic asymmetry. As described in the zebrafish, we have sequenced RNAs extracted from serial sections along transverse, horizontal and sagittal planes, mapped the data onto a gene reference taking advantage of the high continuity genome recently released in the catshark, and projected read counts onto a digital model of the head obtained by confocal microscopy.

Recent Advances on -Ethoxycarbonyl and -Acyl Protected Cyanohydrins.

Ethoxycarbonyl cyanohydrins and -acyl cyanohydrins are examples of -protected cyanohydrins in which the protecting group presents an electrophilic center, contributing to additional reaction pathways. The first section of this review describes recent advances on the synthesis of -ethoxycarbonyl and -acyl protected cyanohydrins. Reactions using KCN or alkyl cyanoformates as the cyanide ion source are described, as well as organic and transition metal catalysis used in their preparation, including asymmetric cyanation.

Cyclometalated Osmium Compounds and beyond: Synthesis, Properties, Applications.

The synthesis of cyclometalated osmium complexes is usually more complicated than of other transition metals such as Ni, Pd, Pt, Rh, where cyclometalation reactions readily occur via direct activation of C-H bonds. It differs also from their ruthenium analogs. Cyclometalation for osmium usually occurs under more severe conditions, in polar solvents, using specific precursors, stronger acids, or bases.

Synthesis of Poly(2-Acrylamido-2-Methylpropane Sulfonic Acid) and its Block Copolymers with Methyl Methacrylate and 2-Hydroxyethyl Methacrylate by Quasiliving Radical Polymerization Catalyzed by a Cyclometalated Ruthenium(II) Complex.

The first example of quasiliving radical polymerization and copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) without previous protection of its strong acid groups catalyzed by [Ru(-CH-2-py)(phen)(MeCN)]PF complex is reported. Nuclear magnetic resonance (RMN) and gel permeation chromatography (GPC) confirmed the diblock structure of the sulfonated copolymers. The poly(2-acryloamido-2-methylpropanesulfonic acid)--poly(methyl methacrylate) (PAMPS--PMMA) and poly(2-acryloamido-2-methylpropanesulfonic acid)--poly(2-hydroxyethylmethacrylate) (PAMPS--PHEMA) copolymers obtained are highly soluble in organic solvents and present good film-forming ability.

Light activation of cyclometalated ruthenium complexes drives towards caspase 3 dependent apoptosis in gastric cancer cells.

Polypyridyl ruthenium complexes have been intensively investigated for their remarkable antiproliferative properties and some are currently being tested in clinical trials. Here, we investigated the impact of illumination on the biological properties of a series of new cyclometalated ruthenium compounds with increased π-conjugation. We determined that various of these complexes display a bivalent biological activity as they are highly cytotoxic by themselves in absence of light while their cytotoxicity can significantly be elevated towards an IC in the nanomolar range upon illumination.

A redox ruthenium compound directly targets PHD2 and inhibits the HIF1 pathway to reduce tumor angiogenesis independently of p53.

Targeting specific tumor metabolic needs represents an actively investigated therapeutic strategy to bypass tumor resistance mechanisms. In this study, we describe an original approach to impact the cancer metabolism by exploiting the redox properties of a ruthenium organometallic compound. This organometallic complex induced p53-independent cytotoxicity and reduced size and vascularization of patients-derived tumor explants that are resistant to platinum drugs.

Neurogenetic asymmetries in the catshark developing habenulae: mechanistic and evolutionary implications.

Analysis of the establishment of epithalamic asymmetry in two non-conventional model organisms, a cartilaginous fish and a lamprey, has suggested that an essential role of Nodal signalling, likely to be ancestral in vertebrates, may have been largely lost in zebrafish. In order to decipher the cellular mechanisms underlying this divergence, we have characterised neurogenetic asymmetries during habenular development in the catshark Scyliorhinus canicula and addressed the mechanism involved in this process. As in zebrafish, neuronal differentiation starts earlier on the left side in the catshark habenulae, suggesting the conservation of a temporal regulation of neurogenesis.

Impact of cyclometalated ruthenium(II) complexes on lactate dehydrogenase activity and cytotoxicity in gastric and colon cancer cells.

Lactate dehydrogenase (LDH) is a redox enzyme often overexpressed in cancer cells allowing their survival in stressful metabolic tumor environment. Ruthenium(II) complexes have been shown to impact on the activity of purified horseradish peroxidase and glucose oxidase but the physiological relevance remains unclear. In this study we investigated how ruthenium complexes impact on the activity of LDH in vitro and in cancer cells and performed a comparative study using polypyridine ruthenium(II) complex [Ru(bpy)] (1) and its structurally related cyclometalated 2-phenylpyridinato counterpart [Ru(phpy)(bpy)] (2) (bpy=2,2'-bipyridine, phpyH=2-phenylpyridine).

Species-specific contribution of volumetric growth and tissue convergence to posterior body elongation in vertebrates.

Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis.

Further Insight into the Lability of MeCN Ligands of Cytotoxic Cycloruthenated Compounds: Evidence for the Antisymbiotic Effect Trans to the Carbon Atom at the Ru Center.

The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) hybridized N atom, cannot be substituted by any other ligand. In contrast, the isomerized derivative [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(MeCN)2]PF6 (2), in which one MeCN ligand is now trans to the C atom of the phenyl ring orthometalated to Ru, leads to fast and quantitative substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(PPh3)(MeCN)]PF6 (3), in which PPh3 is trans to the C σ bound to Ru.

Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula.

The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.

The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain.

Left-right asymmetries in the epithalamic region of the brain are widespread across vertebrates, but their magnitude and laterality varies among species. Whether these differences reflect independent origins of forebrain asymmetries or taxa-specific diversifications of an ancient vertebrate feature remains unknown. Here we show that the catshark Scyliorhinus canicula and the lampreys Petromyzon marinus and Lampetra planeri exhibit conserved molecular asymmetries between the left and right developing habenulae.