Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis.

Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.

Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents.

A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a-7a, 1b-7b, 1c-7c, 1d-7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC50=0.86µM for Hela and IC50=0.12µM for EGFR). Structure-activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (-OCH3>-CH3>-H>-Br>-Cl>-F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p-π bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent.

Synthesis, molecular docking and biological evaluation of glycyrrhizin analogs as anticancer agents targeting EGFR.

Glycyrrhizin (GA) analogs in the form of 3-glucuronides and 18-epimers were synthesized and their anticancer activities were evaluated. Alkaline isomerization of monoglucuronides is reported. In vitro and in vivo studies showed that glycyrrhetinic acid monoglucuronides (GAMGs) displayed higher anticancer activities than those of bisglucuronide GA analogs, while anticancer activity of the 18α-epimer was superior to that of the 18ß-epimer. 18α-GAMG was firstly nicely bound to epidermal growth factor receptor (EGFR) via six hydrogen bonds and one charge interaction, and the docking calculation proved the correlation between anticancer activities and EGFR inhibitory activities. Highly active 18α-GAMG is thus of interest for the further studies as a potential anticancer agent.

Synthesis of caffeic acid amides bearing 2,3,4,5-tetra-hydrobenzo[b][1,4]dioxocine moieties and their biological evaluation as antitumor agents.

A series of caffeic acid amides D1-D17 bearing 2,3,4,5-tetrahydrobenzo-[b][1,4]dioxocine units has been synthesized and their biological activities evaluated for potential antiproliferative and EGFR inhibitory activity. Of all the compounds studied, compound D9 showed the most potent inhibitory activity (IC50=0.79 µM for HepG2 and IC50=0.36 µM for EGFR). The structures of compounds were confirmed by 1H-NMR, ESI-MS and elemental analysis. Among all, the structure of compound D9 ((E)-N-(4-ethoxyphenyl)-3-(2,3,4,5-tetrahydrobenzo[b][1,4]dioxocin-8-yl)acrylamide) was also determined by single-crystal X-ray diffraction analysis. Compound D9 was found to be a potential antitumor agent according to biological activity, molecular docking, apoptosis assay and inhibition of HepG2.

Tetra-aqua-bis[2-(2,4-dichloro-phen-oxy)acetato]nickel(II).

In the title complex, [Ni(C(8)H(5)Cl(2)O(3))(2)(H(2)O)(4)], the Ni(II) atom (site symmetry ) adopts a slightly distorted NiO(6) octa-hedral coordination. An intra-molecular O-H⋯O hydrogen bond helps to establish the conformation. In the crystal, further O-H⋯O hydrogen bonds link the mol-ecules.

Bis{2-[3-(dimethyl-amino)propyl-imino-meth-yl]-4,6-dihydro-seleno-phenolato}zinc(II).

In the title complex, [Zn(C(12)H(17)N(2)OSe(2))(2)], the Zn(II) ion is six-coordinated by two N,N',O-tridentate Schiff base ligands, resulting in a slightly distorted trans-ZnO(2)N(4) octa-hedral coordination for the metal ion.

4,4',6,6'-Tetra-hydro-seleno-2,2'-[(E,E)-cyclo-hexane-1,2-diylbis(nitrilo-methyl-idyne)]diphenol.

In the title mol-ecule, C(20)H(22)N(2)O(2)Se(4), the dihedral angle between the pendant aromatic rings is 67.1 (2)°. The conformation is stabilized by two intra-molecular O-H⋯N hydrogen bonds.

Construction of N-containing heterocycles via oxidative intramolecular N-H/X-H coupling.

The preparation of N-containing heterocycles is always the core of synthetic chemistry. Recently, oxidative coupling between two R-H nucleophiles is gaining more attention due to its atom-economy and step-economy, thus there are numerous reports focusing on the N-heterocycle construction via oxidative coupling. This feature article is going to cover the methodology related to the construction of N-heterocycles through oxidative intramolecular N-H/X-H coupling.

Bimetallic zinc complex--active species in coupling of terminal alkynes with aldehydes via nucleophilic addition/Oppenauer oxidation.

A mechanistic study on the zinc-promoted coupling between aldehydes and terminal alkynes via nucleophilic addition/Oppenauer oxidation using operando IR, XANES/EXAFS techniques and DFT calculations was demonstrated. It was determined that a bimetallic zinc complex was the active species.

Fe-Catalysed oxidative C-H/N-H coupling between aldehydes and simple amides.

A novel oxidative coupling of aldehydes with simple amides, most likely involving a radical process, was achieved through the use of an iron catalyst. Various amides were utilized as substrates to easily construct imides by coupling with aldehydes. A catalytic cycle involving the benzoyl halide intermediate is proposed based on our experimental results.

Direct oxidative esterification of alcohols.

Esterification is a fundamental transformation in chemistry. Traditional esterification only largely occurs between carboxylic acid derivatives and alcohols, and often involves multistep processes. Developments in the transition-metal-catalysed and metal-free direct esterification of alcohols under oxidative conditions has opened a door to the efficient, sustainable and environmentally friendly synthesis of esters from readily available materials. This Perspective gives an overview which covers the recent development of this emerging field.

I2-catalyzed oxidative C(sp³)-H/S-H coupling: utilizing alkanes and mercaptans as the nucleophiles.

By using alkanes and mercaptans as the nucleophiles with di-tert-butyl peroxide (DTBP) as the oxidant, I2-catalyzed oxidative C(sp(3))-H/S-H coupling was achieved. This protocol provides a novel process to construct C(sp(3))-S bonds from commercially available hydrocarbons and mercaptans.