Electrochemical Oxidative Difunctionalization of Diazo Compounds with Diselenides and Nucleophiles.

An electrochemical oxidative difunctionalization of diazo compounds with diselenides and nucleophiles has been developed. This innovative approach yields a diverse array of selenium-containing pyrazole esters and alkoxy esters, overcoming the limitations of traditional synthesis methods. Remarkably, various nucleophiles, including acids, alcohols, and pyrazoles, can be seamlessly incorporated. Notably, this protocol boasts high atom efficiency, excellent functional group tolerance, and good efficiency and operates under transition metal- and oxidant-free conditions, distinguishing it in the field.

Electrochemical selenium-catalyzed para-amination of N-aryloxyamides: access to polysubstituted aminophenols.

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

Synthesis of Selenyl-Substituted Quinoline Derivatives via Substrate-Controlled Three-Component Domino Reactions.

A simple and efficient method for the preparation of selenyl-substituted quinoline derivatives through a CSp3-H selenylation of in situ-generated 3-acetyl quinoline has been developed. This protocol is easy to handle, scalable, and good functional group tolerant, providing a rapid method to 3-selenoacetyl quinoline and 3-diselenoacetyl quinoline derivatives.

Electrochemically enabled functionalization of indoles or anilines for the synthesis of hexafluoroisopropoxy indole and aniline derivatives.

An environmentally benign electrochemically enabled site-selective functionalization of indole or aniline derivatives with hexafluoroisopropanol in the presence of tetrabutyl ammonium hexafluorophosphate as the redox catalyst and electrolyte was demonstrated in this work. Under mild electro-oxidation conditions, a series of hexafluoroisopropoxy indole and aniline derivatives with pharmacological activity were obtained. This conversion does not need transition metals and oxidants, and has good functional group tolerance. The in vitro cytotoxicity of all compounds was evaluated by the MTT assay against four human cancer cell lines. The results revealed that hexafluoroisopropoxy indoles have good antitumor activity and compound 2i increased the intracellular levels of ROS and inhibited apoptosis in HeLa cells.

Visible-Light-Promoted Selenylative Spirocyclization of Indolyl-ynones toward the Formation of 3-Selenospiroindolenine Anticancer Agents.

A metal-free and efficient visible-light-induced spirocyclization of indolyl-ynones with diselenides at room temperature under air atmosphere to prepare 3-selenospiroindolenines in moderate to good yields has been developed. The resulting products were tested for in vitro anticancer activity by MTT assay, and compounds 3 c and 3 e showed potent cancer cell-growth inhibition activities.

Electrochemical Synthesis of 1-Naphthols by Intermolecular Annulation of Alkynes with 1,3-Dicarbonyl Compounds.

C-centered radical cyclization under electrochemical conditions is a feasible strategy for constructing cyclic structures. Reported herein is the electrochemical synthesis of highly functionalized 1-naphthols using alkynes and 1,3-dicarbonyl compounds by (4 + 2) annulation of C-centered radical. Electrolysis was conducted with Cp2Fe as redox catalyst, thereby eliminating the use of oxidants and transition-metal catalysts. The synthesized 1-naphthol compounds showed good antitumor activity in vitro, and further studies indicated that compound 3bl induced tumor cell apoptosis.

Electrochemically Enabled Double C-H Activation of Amides: Chemoselective Synthesis of Polycyclic Isoquinolinones.

We developed an electrochemically enabled dehydrogenative annulation reaction of amides and alkynes for the synthesis of antitumor polycyclic isoquinolinones through a double C-H activation route. No external oxidant is required in this reaction, and electricity is used for Ru catalyst circulation. The most remarkable feature of this reaction is the effective improvement of product regioselectivity under mild electrolytic conditions in comparison with previously set strong oxidant conditions.

Photocatalytic Construction of S-S and C-S Bonds Promoted by Acridinium Salt: An Unexpected Pathway To Synthesize 1,2,4-Dithiazoles.

An unexpected cyclization of thioamides with p-quinone methides promoted by acridinium salt under the irradiation of visible light furnished 1,2,4-dithiazoles in moderate to good yields. In addition, the reaction of the obtained 1,2,4-dithiazoles with isocyanides offered a new entry for the synthesis of thiazol-5(4 H)-imines in moderate yields.

RankProd Combined with Genetic Algorithm Optimized Artificial Neural Network Establishes a Diagnostic and Prognostic Prediction Model that Revealed C1QTNF3 as a Biomarker for Prostate Cancer.

Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the Western world. Although prostate-specific antigen (PSA) has been widely used as a biomarker for PCa diagnosis, its results can be controversial. Therefore, new biomarkers are needed to enhance the clinical management of PCa. From publicly available microarray data, differentially expressed genes (DEGs) were identified by meta-analysis with RankProd. Genetic algorithm optimized artificial neural network (GA-ANN) was introduced to establish a diagnostic prediction model and to filter candidate genes. The diagnostic and prognostic capability of the prediction model and candidate genes were investigated in both GEO and TCGA datasets. Candidate genes were further validated by qPCR, Western Blot and Tissue microarray. By RankProd meta-analyses, 2306 significantly up- and 1311 down-regulated probes were found in 133 cases and 30 controls microarray data. The overall accuracy rate of the PCa diagnostic prediction model, consisting of a 15-gene signature, reached up to 100% in both the training and test dataset. The prediction model also showed good results for the diagnosis (AUC = 0.953) and prognosis (AUC of 5 years overall survival time = 0.808) of PCa in the TCGA database. The expression levels of three genes, FABP5, C1QTNF3 and LPHN3, were validated by qPCR. C1QTNF3 high expression was further validated in PCa tissue by Western Blot and Tissue microarray. In the GEO datasets, C1QTNF3 was a good predictor for the diagnosis of PCa (GSE6956: AUC = 0.791; GSE8218: AUC = 0.868; GSE26910: AUC = 0.972). In the TCGA database, C1QTNF3 was significantly associated with PCa patient recurrence free survival (P < .001, AUC = 0.57). In this study, we have developed a diagnostic and prognostic prediction model for PCa. C1QTNF3 was revealed as a promising biomarker for PCa. This approach can be applied to other high-throughput data from different platforms for the discovery of oncogenes or biomarkers in different kinds of diseases.

Palladium-Metalated Porous Organic Polymers as Recyclable Catalysts for the Chemioselective Synthesis of Thiazoles from Thiobenzamides and Isonitriles.

Two types of thiazole derivatives are synthesized through a multistep cascade sequence with Pd-metalated phosphorus-doped porous organic polymers (POPs) as heterogeneous catalysts. The POPs could be used as both ligands and catalyst supports. No obvious aggregation and loss of any catalytic activity of the catalysts were observed after 10 runs of the reaction. More importantly, imidazo[4,5- d]thiazoles, which are a new class of thiazole derivatives, could be obtained through K2CO3-promoted intramolecular cyclization of the synthesized polysubstituted thiazoles. Furthermore, the in vitro anticancer activity of these new compounds were tested with MTT assay, and compound 4b exhibited good antitumor activity toward T-24 and A549 cells with IC50 values of 10.3 ± 0.8 and 11.8 ± 0.5 µM, respectively. In addition, the action mechanism of 4b on tumor cells was determined.

Copper-Catalyzed Decarboxylative/Click Cascade Reaction: Regioselective Assembly of 5-Selenotriazole Anticancer Agents.

A simple and efficient Cu-catalyzed decarboxylative/click reaction for the preparation of 1,4-disubstituted 5-arylselanyl-1,2,3-triazoles from propiolic acids, diselenides, and azides has been developed. The mechanistic study revealed that the intermolecular AAC reaction of an alkynyl selenium intermediate occurred. The resulting multisubstituted 5-seleno-1,2,3-triazoles were tested for in vitro anticancer activity by MTT assay, and compounds 4f, 4h, and 4p showed potent cancer cell-growth inhibition activities.

GSTM1 and GSTT1 polymorphisms contribute to renal cell carcinoma risk: evidence from an updated meta-analysis.

Emerging evidences suggest that GSTM1 and GSTT1 are involved in the detoxification of carcinogens, and polymorphisms in this gene that result in a loss of enzyme activity may increase the risk of renal cell carcinoma (RCC). Thus, to evaluate the association of GSTM1 and GSTT1 polymorphisms and RCC, we performed an updated meta-analysis of 10 case-control studies by RevMan 5.2, and the publication bias was tested using STATA 11.0. The meta-analysis showed that the single locus GSTM1 and GSTT1 polymorphisms were not significantly associated with a risk of RCC in a recessive model. However, that wild-type genotype versus the dual null genotype of GSTM1-GSTT1 showed a positive association with RCC risk (OR = 0.70; 95% CI = 0.51-0.98; P = 0.04). In another analysis of subjects exposed to pesticides, we found that the GSTM1 wild-type genotype was associated with increased RCC risk in Europeans (OR = 2.72; 95% CI = 1.54-4.82; P = 0.0006). We also identified an association between the GSTT1 wild-type and lower RCC TNM staging (I + II versus III + IV: OR = 1.88; 95% CI = 1.09-3.26; P = 0.02). This meta-analysis suggests that there may be a relationship between the GSTM1 and GSTT1 wild-type genotype and RCC.

[Association of 5-hydroxytryptamine transporter gene polymorphism with asthma and comorbid depression].

OBJECTIVE: To explore the molecular genetic mechanism of complicating depression in asthma by detecting two gene polymorphisms of 5-hydroxytryptamine transporter (5-HTTLPR/Stin2) gene. METHODS: One hundred fifty-six adults with asthma were collected, and divided into group of asthma with depression (HAMD score > or = 8) and group of asthma without depression or single asthma (HAMD score <8) according to the score of Hamilton depression scale (HAMD). A total of 508 adults with depression alone and 433 healthy individuals were enrolled as controls. The target gene fragments containing the polymorphic regions of 5-HTTLPR and Stin2 were amplified by polymerase chain reaction (PCR). The amplified fragments were then analyzed using agarose gel electrophoresis (AGE) and motored molecular imaging system. RESULTS: The frequencies of genotype and allele distribution of the Stin2 polymorphism showed that males with genotype Stin2.12/Stin2.10 and allele Stin2.10 had higher risk for asthma than the others (Stin2.12/Stin2.10: OR = 2.291, 95% CI: 1.195 and 4.390; Stin2.10: OR = 1.942, 95% CI: 1.069-3.527). No significant difference was found in the frequencies of genotype and allele distribution of the 5-HTTLPR locus between the asthma and healthy control groups and the two stratified by gender. CONCLUSION: The Stin2 polymorphism may play a role in the onset of male asthma. There might be association between the genetic pathogenesis of asthma and depression.

[The study on relationship between negative mood states and asthma control and quality of life].

OBJECTIVE: To explore the relationship between psychological status including depression and anxiety, and asthma control and quality of life. METHODS: A brief, structured psychiatric interview using the Hamilton depression scale (HAMD) and the Hamilton anxiety scale (HAMA) were applied to 156 consecutive adults with confirmed, physician-diagnosed asthma. Asthma control and asthma-related quality of life were assessed using the asthma control questionnaire (ACQ) and the asthma quality of life questionnaire (AQLQ). Detection of FEV1, FVC and PEF with standard spirometry for all patients was conducted. The patients were divided into depression (DG), anxiety (AG), depression and anxiety (ADG), and non depression and/or non anxiety (NADG) groups according to the scores for depression and anxiety degree. Level of asthma control, quality of life and pulmonary function of different groups were compared and a multiple regression model was set for the analisis. RESULTS: Sixty five percent of patients (n=101) had symptoms of depression or anxiety (18% had depression, 5% had anxiety, and 42% had both). Analyses revealed independent effects for depression but not anxiety, on total ACQ and AQLQ scores (both P<0.05). Moreover, there was no interaction effects on anxiety and depression coupled with anxiety. CONCLUSION: It suggests that depression but not anxiety, is associated with worse asthma control and asthma-related quality of life. Physicians should consider the differential impact of negative mood states when assessing levels of asthma control and quality of life.