Hydrogen Sulfide Prodrugs—A review

Abstract Hydrogen sulfide (H2S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H2S prodrugs for various reasons. In this review, we summarize different H2

Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

AbstractA novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71 (EV71) and the coxsackievirus B3 (CVB3) and B6 (CVB6) were evaluated. Compounds 7d and 9b showed potent antiviral activities against EV71 with IC50 values of 8.27 and 5.48μM, respectively. Compound 7f, which has been synthesized for the first time in this work, showed the highest level of inhibitory activity against both CVB3 and CVB6 with an IC50 value of 0.62 and 0.87μM. Compounds 4b, 7a, 9c and 9e also showed strong inhibitory activities against both the CVB3 and CVB6 at low concentrations (IC50=1.42−7.15μM), whereas compounds 4d, 7c, 7e and 7g showed strong activity against CVB6 (IC50=2.91–3.77μM) together with low levels of activity against CVB3. Compound 7d exhibited stronger inhibitory activity against CVB3 (IC50=6.44μM) than CVB6 (IC50>8.29μM). The thioflavone derivatives 7a, 7c, 7d, 7e, 7f and 7g, represent a new class of lead compounds for the development of novel antiviral agents

A Small Molecule Antagonist of SMN Disrupts the Interaction Between SMN and RNAP II

Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase II subunit POLR2A, resulting in transcription termination and R-loop accumulation mimicking SMN depletion. Thus, in addition to the antisense, RNAi and CRISPR/Cas9 techniques, potent SMN antagonists could be used as an efficient tool to understand the biological functions of SMN

Experimental study on light induced influence model to mice using support vector machine

Previous researchers have made studies on different influences created by light irradiation to animals, including retinal damage, changes of inner index and so on. However, the model of light induced damage to animals using physiological indicators as features in machine learning method is never founded. This study was designed to evaluate the changes in micro vascular diameter, the serum absorption spectrum and the blood flow influenced by light irradiation of different wavelengths, powers and exposure time with support vector machine (SVM). The micro images of the mice auricle were recorded and the vessel diameters were calculated by computer program. The serum absorption spectrums were analyzed. The result shows that training sample rate 20% and 50% have almost the same correct recognition rate. Better performance and accuracy was achieved by third-order polynomial kernel SVM quadratic optimization method and it worked suitably for predicting the light induced damage to organisms

(E)-2-Hydroxy-4-methoxy-3-(3-methylbut-2-enyl)-6-styrylbenzoic acid

The title compound, C21H22O4, also known as cajanine, features an intramolecular O—H...O hydrogen bond between the adjacent carboxy and hydroxy groups. The benzene rings make an interplanar angle of 175.4 (2)°. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers

Organic CO Prodrugs Activated by Endogenous ROS

CO prodrugs with triggered release mechanisms are highly desirable for targeted delivery. Herein described are organic CO prodrugs that are activated by ROS and thus can be used to selectively deliver CO to cells with elevated ROS levels. Such CO prodrugs can serve as powerful tools for targeted delivery to disease sites with elevated ROS levels and to explore the therapeutic applications of CO

Cholinergic basal forebrain atrophy in Parkinson's disease with freezing of gait

Abstract Background Mounting research support that cholinergic dysfunction plays a prominent role in freezing of gait (FOG), which commonly occurs in Parkinson's disease (PD). Basal forebrain (BF), especially the cholinergic nuclei 4 (Ch4), provides the primary source of the brain cholinergic input. However, whether the degeneration of BF and its innervated cortex contribute to the pathogenesis of FOG is unknown. Objective To explore the role of structural alterations of BF and its innervated cortical brain regions in the pathogenesis of PD patients with freezing. Methods Magnetic resonance imaging assessments and neurological assessments were performed on 20 PD patients with FOG (PD‐FOG), 20 without FOG (PD‐NFOG), and 21 healthy participants. Subregion volumes of the BF were compared among groups. Local gyrification index (LGI) was computed to reveal the cortical alternations. Relationships among subregional BF volumes, LGI, and the severity of FOG were evaluated by multiple linear regression. Results Our study discovered that, compared to PD‐NFOG, PD‐FOG exhibited significant Ch4 atrophy (p = 4.6 × 10−5), accompanied by decreased LGI values in the left entorhinal cortex (p = 3.00 × 10−5) and parahippocampal gyrus (p = 2.90 × 10−5). Based on the regression analysis, Ch4 volume was negatively associated with FOG severity in PD‐FOG group (β = −12.224, T = −2.556, p = 0.031). Interpretation Our results imply that Ch4 degeneration and microstructural disorganization of its innervated cortical brain regions may play important roles in PD‐FOG

Click and Fluoresce: A Bioorthogonally Activated Smart Probe for Wash-Free Fluorescent Labeling of Biomolecules

Bioorthogonally activated smart probes greatly facilitate the selective labeling of biomolecules in living system. Herein, we described a novel type of smart probes with tunable reaction rates, high fluorescence turn-on ratio, and easy access. The practicality of such probes was demonstrated by selective labeling of lipid and hCAII in Hela cells