Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role played by substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease expression of cardiac hypertrophy and oxidative stress related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.
Water-soluble small organic photothermal agents (PTAs) over NIR-II biowindow (1000-1350 nm) are highly desirable, but the rarity greatly limits their applications. Based on a water-soluble double-cavity cyclophane GBox-44+ , we report a class of host-guest charge transfer (CT) complexes as structurally uniform PTAs for NIR-II photothermal therapy. As a result of its high electron-deficiency, GBox-44+ can bind different electron-rich planar guests with a 1 : 2 host/guest stoichiometry to readily tune the CT absorption band that extends to the NIR-II region. When using a diaminofluorene guest substituted with an oligoethylene glycol chain, the host-guest system realized both good biocompatibility and enhanced photothermal conversion at 1064 nm, and was then exploited as a high-efficiency NIR-II PTA for cancer cell and bacterial ablation. This work broadens the potential applications of host-guest cyclophane systems and provides a new access to bio-friendly NIR-II photoabsorbers with well-defined structures.
Two metal–organic framework compounds composed of cerium ions coordinated with tetra(4-carboxyphenyl) porphyrin H2TCPP (3) and its cobalt congener CoTCPP (4), namely H2TCPP/Ce (1) and CoTCPP/Ce (2) were synthesized. Their self-assembly behaviors were systematically investigated using electronic absorption spectra, scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and energy dispersive X-ray spectroscopy (EDX). The formation of H2TCPP/Ce (1) nanoparticles with an average diameter of 500 nm depended mainly on the Ce–O coordination bond between the additive cerium ion and the oxygen atom of the carboxy group of the porphyrin 3 molecule. However, additionally formed Co–C coordination bonds between the central cobalt ion of 4 to the carbon atom of the adjacent porphyrinato 4 ring, in combination with Ce–O coordination bond between the additive cerium ion and the oxygen atom of the carboxy group of porphyrinato 4 molecules, induced the formation of CoTCPP/Ce (2) nanoparticles with apparently smaller average diameters (380 nm). After calcining the corresponding H2TCPP/Ce (1) and CoTCPP/Ce (2) metal–organic frameworks, two types of morphology-preserved CeO2 were obtained, both of which showed excellent catalytic properties towards the oxidation of CO to CO2.
Abstract The stereoselectivity of the N‐glycosylation reaction of purines and uracils with hexynylbenzoate (I) depends on the concentration of the reaction solution leading to higher β/α‐ratio at lower concentrations.
Tandem mass spectrometry (MS/MS) acts as a key technique for peptide identification. The MS/MS-based peptide identification approaches can be categorized into two families, namely, de novo and database search. Both of the two types of approaches can benefit from an accurate prediction of theoretical spectrum. A theoretical spectrum consists of m/z and intensity of possibly occurring ions, which are estimated via simulating the spectrum generating process. Extensive researches have been conducted for theoretical spectrum prediction; however, the prediction methods suffer from low prediciton accuracy due to oversimplifications in the spectrum simulation process.In the study, we present an open-source software package, called OpenMS-Simulator, to predict theoretical spectrum for a given peptide sequence. Based on the mobile-proton hypothesis for peptide fragmentation, OpenMS-Simulator trained a closed-form model for the intensity ratio of adjacent y ions, from which the whole theoretical spectrum can be constructed. On a collection of representative spectra datasets with annotated peptide sequences, experimental results suggest that OpenMS-Simulator can predict theoretical spectra with considerable accuracy. The study also presents an application of OpenMS-Simulator: the similarity between theoretical spectra and query spectra can be used to re-rank the peptide sequence reported by SEQUEST/X!Tandem.OpenMS-Simulator implements a novel model to predict theoretical spectrum for a given peptide sequence. Compared with existing theoretical spectrum prediction tools, say MassAnalyzer and MSSimulator, our method not only simplifies the computation process, but also improves the prediction accuracy. Currently, OpenMS-Simulator supports the prediction of CID and HCD spectrum for peptides with double charges. The extension to cover more fragmentation models and support multiple-charged peptides remains as one of the future works.
A syn-atropisomer precursor was employed to construct trapezoid-shape macrocycles, which can selectively recognize tryptophan from 20 standard amino acids.
Benzylic halides were successfully oxidized to the corresponding aldehydes and ketones in good to excellent yields in aqueous media with molecular oxygen as oxidant in the presence of catalytic amounts of TEMPO (2,2,6,6-tetramethylpiperidyl-1-oxy) and potassium nitrite (KNO2).
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