Structure-Activity Relationship of Benzophenazine Derivatives for Homogeneous and Heterogenized Photooxygenation Catalysis.

Singlet oxygen is a powerful oxidant used in various applications, such as organic synthesis, medicine, and environmental remediation. Organic and inorganic photosensitizers are commonly used to generate this reactive species through energy transfer with the triplet ground state of oxygen. We describe here a series of novel benzophenazine derivatives as a promising class of photosensitizers for singlet oxygen photosensitization.

A novel approach to pH-Responsive targeted cancer Therapy: Inhibition of FaDu cancer cell proliferation with a pH low insertion Peptide-Conjugated DGAT1 inhibitor.

Targeting enzymes involved in lipid metabolism is increasingly recognized as a promising anticancer strategy. Efficient inhibition of diacylglycerol O-transferase 1 (DGAT1) can block fatty acid (FA) storage. This, in turn, triggers an increase in free polyunsaturated FA concentration, leading to peroxidation and ferroptosis.

The crane fly glycosylated triketide δ-lactone cornicinine elicits akinete differentiation of the cyanobiont in aquatic Azolla fern symbioses.

The restriction of plant-symbiont dinitrogen fixation by an insect semiochemical had not been previously described. Here we report on a glycosylated triketide δ-lactone from Nephrotoma cornicina crane flies, cornicinine, that causes chlorosis in the floating-fern symbioses from the genus Azolla. Only the glycosylated trans-A form of chemically synthesized cornicinine was active: 500 nM cornicinine in the growth medium turned all cyanobacterial filaments from Nostoc azollae inside the host leaf-cavities into akinetes typically secreting CTB-bacteriocins.

Valorization of Chicken Viscera as Natural Raw Material Source: Application to Hydrolysis of Fatty Esters for Sewage Treatment.

"Chicken viscera" constitutes very abundant domestic wastes interestingly investigated in the present paper. The efficiency of this crude slaughter co-product of high protein component, as biocatalyst, for the hydrolysis of fatty acid esters was reported and that, without any pre-treatment. The crude chicken intestine powder (CIP) has shown a high reactivity for the hydrolysis of fatty esters.

Enhancing Tsuji-Trost deallylation in living cells with an internal-nucleophile coumarin-based probe.

In recent years, bioorthogonal uncaging reactions have been developed to proceed efficiently under physiological conditions. However, limited progress has been made in the development of protecting groups combining stability under physiological settings with the ability to be quickly removed bioorthogonal catalysis. Herein, we present a new water-soluble coumarin-derived probe bearing an internal nucleophilic group capable of promoting Tsuji-Trost deallylation under palladium catalysis.

Photo-Catalyzed α-Arylation of Enol Acetate Using Recyclable Silica-Supported Heteroleptic and Homoleptic Copper(I) Photosensitizers.

Earth-abundant photosensitizers are highly sought after for light-mediated applications, such as photoredox catalysis, depollution and energy conversion schemes. Homoleptic and heteroleptic copper(I) complexes are promising candidates in this field, as copper is abundant and the corresponding complexes are easily obtained in smooth conditions. However, some heteroleptic copper(I) complexes suffer from low (photo)stability that leads to the gradual formation of the corresponding homoleptic complex.

Discovery of Mitochondrial Complex I Inhibitors as Anticancer and Radiosensitizer Drugs Based on Compensatory Stimulation of Lactate Release.

Cancer cells may stimulate glycolytic flux when O becomes insufficient. Increase in L-lactate release therefore appears as an escape mechanism to drugs targeting mitochondrial respiration but also represents a response that may be exploited to screen for compounds blocking either mitochondrial carriers of oxidizable substrates or the electron transport chain. Here, we developed a screening procedure based on the capacity of cancer cells to release L-lactate to gain insights on the development of mitochondrial complex I inhibitors.

Targeting cancer cells in acidosis with conjugates between the carnitine palmitoyltransferase 1 inhibitor etomoxir and pH (low) insertion peptides.

Targeting enzymes involved in tumor metabolism is a promising way to tackle cancer progression. The inhibition of carnitine palmitoyltransferase 1 (CPT1) by etomoxir (Eto) efficiently slows down the growth of various cancers. Unfortunately, the clinical use of this drug was abandoned because of hepatotoxic effects.

Photodynamic Therapy-Based Dendritic Cell Vaccination Suited to Treat Peritoneal Mesothelioma.

The potential of dendritic cell (DC)-based immunotherapy to treat cancer is, nowadays, well documented. Still, the clinical success of immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening tumors that are regarded as nonimmunogenic, such as mesothelioma, however, T helper 1 immunity-biased DC-based immunotherapy could still represent an attractive strategy.

Re-Evaluating the Mechanism of Action of α,β-Unsaturated Carbonyl DUB Inhibitors b-AP15 and VLX1570: A Paradigmatic Example of Unspecific Protein Cross-linking with Michael Acceptor Motif-Containing Drugs.

Deubiquitinating enzymes (DUBs) are a growing target class across multiple disease states, with several inhibitors now reported. b-AP15 and VLX1570 are two structurally related USP14/UCH-37 inhibitors. Through a proteomic approach, we demonstrate that these compounds target a diverse range of proteins, resulting in the formation of higher molecular weight (MW) complexes.

Kolbe Anodic Decarboxylation as a Green Way To Access 2-Pyrrolidinones.

Nootropic compounds are a group of pharmacologically active pyrrolidones. These molecules, which enhance cognition properties and possess a large prescription field, are particularly interesting synthetic targets for the pharmaceutical industry. In this Article, we disclose an effective and environmentally friendly pyrrolidinone synthesis using electrosynthesis.

A radical exchange process: synthesis of bicyclo[1.1.1]pentane derivatives of xanthates.

Bicyclo[1.1.1]pentane (BCP) replacement as a bioisostere in drug molecules has an influence on their permeability, aqueous solubility and in vitro metabolic stability.

Low Photosensitizer Dose and Early Radiotherapy Enhance Antitumor Immune Response of Photodynamic Therapy-Based Dendritic Cell Vaccination.

Recent studies have highlighted the potential of photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The clinical use of photosensitizers (PS) to stimulate an anticancer immune response, and not to sterilize tumor cells, may however require some optimizations. Here, we examined how the dose of PS and the scheduling of PDT influence the generation of danger-associated molecular patterns proteins (DAMPs) and favor T cell antitumor activity.

Carbon-Nanotube-Appended PAMAM Dendrimers Bearing Iron(II) α-Keto Acid Complexes: Catalytic Non-Heme Oxygenase Models.

Poly(amidoamine) dendrimers grafted on carbon nanotubes have been appended with iron(II)-α-keto acid (benzoylformate) complex of polypyridyl ligand to design artificial non-heme oxygenase model. This nano-enzyme was applied for selective catalytic oxidation of organic molecules. Although the carbon nanotubes serve as a robust heterogeneous platform, the amine terminals of dendrimers provide catalysts binding sites and the amide bonds provide a necessary second coordination sphere similar to the enzymatic polypeptide chains.

Enantio-, Regio- and Chemoselective Copper-Catalyzed 1,2-Hydroborylation of Acylsilanes.

Enantioselective synthesis of synthetically significant (α-hydroxyallyl)silanes, (α-hydroxyaryl)silanes, and (α-hydroxyalkyl)silanes is reported. The present copper-catalyzed 1,2-selective hydroborylation of acylsilanes affords the aforementioned products in high yields and with high enantiomeric excesses. This robust and scalable additive-free catalytic system relies on the use of low copper(II) acetate and diphosphine ligand loadings at room temperature in the presence of a commercially available and bench-stable hydride source.

Covalent Grafting of BPin functions on Carbon Nanotubes and Chan-Lam-Evans Post-Functionalization.

The chemical functionalization of carbon nanotubes is often a prerequisite prior to their use in various applications. The covalent grafting of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (BPin) functional groups directly on the surface of multi- and single-walled carbon nanotubes, activated by nucleophilic addition of nBuLi, was carried out. Thermogravimetric analysis (TGA) coupled with mass spectrometry, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ions mass spectrometry (ToF-SIMS) confirmed the efficiency of this methodology and proved the integrity and covalent grafting of the BPin functional groups.

Preclinical Evaluation of White Led-Activated Non-porphyrinic Photosensitizer OR141 in 3D Tumor Spheroids and Mouse Skin Lesions.

Photodynamic therapy (PDT) is used to treat malignancies and precancerous lesions. Near-infrared light delivered by lasers was thought for a while to be the most appropriate option to activate photosensitizers, mostly porphyrins, in the depth of the diseased tissues. More recently, however, several advantages including low cost and reduced adverse effects led to consider light emitting diodes (LED) and even daylight as an alternative to use PDT to treat accessible lesions.

Synthesis and Catalytic Applications of Multi-Walled Carbon Nanotube-Polyamidoamine Dendrimer Hybrids.

Polyamidoamine (PAMAM) dendrimers were covalently immobilized on multi-walled carbon nanotubes (MWNT) by two "grafting to" strategies. We demonstrate the existence of non-covalent interactions between the two components but outline the superiority of our two grafting approaches, namely xanthate and click chemistry. MWNT surfaces were functionalized with activated ester and propargylic moieties prior to their reaction with PAMAM or azido-PAMAM dendrimers, respectively.

Biosynthesis of the nickel-pincer nucleotide cofactor of lactate racemase requires a CTP-dependent cyclometallase.

Bacterial lactate racemase is a nickel-dependent enzyme that contains a cofactor, nickel pyridinium-3,5-bisthiocarboxylic acid mononucleotide, hereafter named nickel-pincer nucleotide (NPN). The LarC enzyme from the bacterium participates in NPN biosynthesis by inserting nickel ion into pyridinium-3,5-bisthiocarboxylic acid mononucleotide. This reaction, known in organometallic chemistry as a cyclometalation, is characterized by the formation of new metal-carbon and metal-sulfur σ bonds.

Copper-Catalyzed One-Pot Borylative Aldolisation β-Fluoride Elimination for the Formal Addition of Acrylates to Carbonyl Moieties.

Herein, we report the copper-catalyzed domino borylation/aldolisation of methyl 2-fluoroacrylate with carbonyl compounds followed by an elimination to give Morita-Baylis-Hillman (MBH) analogues. The optimal conditions described were shown to be compatible with a wide range of aldehydes and ketones. Unprecedented MBH adducts derived from ketones were efficiently synthesized.

Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects.

Lactate exchange between glycolytic and oxidative cancer cells is proposed to optimize tumor growth. Blocking lactate uptake through monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic strategy but may stimulate glucose consumption by oxidative cancer cells. We report here that inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks of blocking lactate use while preventing glucose oxidative metabolism.

Validation of a SPE HPLC-UV method for the quantification of a new ER-specific photosensitizer OR-141 in blood serum using total error concept.

The aim of this work is to develop the first validated HPLC-UV method quantification in blood serum for a new endoplasmic reticulum (ER)-specific benzophenazine photosensitizer (OR-141). A fast solid phase extraction (SPE) cleaning sample procedure was achieved on C18 encapped (ec) SPE cartridges and the separation was performed on a RP-18e column (5μM) using an isocratic elution with methanol. The method has been fully validated according to accuracy profiles based on total error and tolerance intervals.

Versatile Two-Step Functionalization of Nanocarbons: Grafting of Propargylic Groups and Click Post-Functionalization.

Chemical functionalization of nanocarbons is essential for further applications in various fields. We developed a facile, inexpensive, and gram-scale one-pot route towards alkynyl-functionalized nanocarbons. Nucleophilic addition/propargylic capture places alkyne moieties at the surface of carbon nanotubes (CNTs) and graphene.