Insular dysfunction of interoception in major depressive disorder: from the perspective of neuroimaging.

Interoception plays a crucial role in maintaining bodily homeostasis and promoting survival, and is considered the basis of human emotion, cognition, and self-formation. A malfunction of interoception is increasingly suggested to be a fundamental component of different mental health conditions, and depressive disorders have been especially closely associated. Interoceptive signaling and processing depends on a system called the "interoceptive pathway," with the insula, located in the deep part of the lateral fissure, being the most important brain structure in this pathway. Neuroimaging studies have revealed alterations in the structure and function of the insula in a large number of individuals with depression, yet the precise relationship between these alterations and interoceptive dysfunction remains unclear. The goal of this review is to examine the evidence that exists for dysfunction of interoception in people with Major Depressive Disorder (MDD), and to determine the associated specific alterations in the structure and function of the insula revealed by neuroimaging. Overall, three aspects of the potential relationship between interoceptive dysfunction and alterations in insular function in people with depression have been assessed, namely clinical symptoms, quantitative measures of interoceptive function and ability, and interoceptive modulation. To conclude, several specific limitations of the published studies and important lines of enquiry for future research are offered.

Electrophilic Thiocyanation of Tryptamine Derivatives: Divergent Synthesis of SCN-Containing Indole Compounds.

A tandem dearomative electrophilic thiocyanation/cyclization/acylation of indoles was developed for the first time, which is enabled by acyl chloride. A variety of 3-SCN pyrroloindolines were obtained with moderate to excellent yields. Interestingly, following replacement of acyl chloride with methanesulfonic acid, 2-SCN tryptamines were obtained using the same starting substrates and reagents. Furthermore, catalytic enantioselective manner of thiocyanation/cyclization/acylation reaction was also studied. An enantiomer self-disproportionation effect of 3-SCN pyrroloindolines was discovered. A series of chiral 3-SCN pyrroloindolines were obtained with high enantioselectivities.

Enhancing the Photoelectric Properties of Zinc Porphyrin Dyes by Introducing Five-Membered Heterocyclic Rings into the Electron Donor: A Density Functional Theory and Time-Dependent Density Functional Theory Study.

To fabricate highly efficient dye sensitizers for dye-sensitized solar cells, new zinc porphyrin dye sensitizers were designed based on one of the most efficient dyes, YD2-o-C8, by introducing electron-rich heterocyclic rings into the electron donor. Five potentially efficient dyes, Dye1-5, were obtained by replacing the phenyl group of the donor in YD2-o-C8 with pyrrolyl, furyl, and thienyl groups. The electronic structures, absorption spectra, intramolecular charge-transfer characteristics, and excited-state lifetimes of the designed dyes were investigated using the density functional theory and time-dependent density functional theory methods. All the designed dyes exhibit better photoelectric properties than those of YD2-o-C8. Compared with YD2-o-C8, the designed new dyes have smaller frontier molecular orbital energy gaps and obvious red-shifting absorption spectra in the Q band. The analyses of charge density difference plots and intramolecular charge-transfer characteristics indicated that the designed dyes can better promote intramolecular charge transfer and electron-hole separation. Among the five designed dyes, Dye1 with a pyrrolyl group exhibits the best performance. Dye3 and Dye5 with methyl-furyl and methyl-thienyl groups, respectively, exhibit the next best performance. Dye2 and Dye4 with furyl and thienyl groups, respectively, are the worst performers. The introduced methyl group can further improve the electron-donating ability of heterocyclic rings and promote the red shift of the Q bands and intramolecular charge transfer of dyes. The excited-state lifetimes of the new dyes were in the following order: YD2-o-C8 < Dye4 < Dye2 < Dye5 < Dye3 < Dye1, which shows their stronger abilities to inject electrons into semiconductor films.

Function-structure coupling: White matter functional magnetic resonance imaging hyper-activation associates with structural integrity reductions in schizophrenia.

White matter (WM) microstructure deficit may be an underlying factor in the brain dysconnectivity hypothesis of schizophrenia using diffusion tensor imaging (DTI). However, WM dysfunction is unclear in schizophrenia. This study aimed to investigate the association between structural deficits and functional disturbances in major WM tracts in schizophrenia. Using functional magnetic resonance imaging (fMRI) and DTI, we developed the skeleton-based WM functional analysis, which could achieve voxel-wise function-structure coupling by projecting the fMRI signals onto a skeleton in WM. We measured the fractional anisotropy (FA) and WM low-frequency oscillation (LFO) and their couplings in 93 schizophrenia patients and 122 healthy controls (HCs). An independent open database (62 schizophrenia patients and 71 HCs) was used to test the reproducibility. Finally, associations between WM LFO and five behaviour assessment categories (cognition, emotion, motor, personality and sensory) were examined. This study revealed a reversed pattern of structure and function in frontotemporal tracts, as follows. (a) WM hyper-LFO was associated with reduced FA in schizophrenia. (b) The function-structure association was positive in HCs but negative in schizophrenia patients. Furthermore, function-structure dissociation was exacerbated by long illness duration and severe negative symptoms. (c) WM activations were significantly related to cognition and emotion. This study indicated function-structure dys-coupling, with higher LFO and reduced structural integration in frontotemporal WM, which may reflect a potential mechanism in WM neuropathologic processing of schizophrenia.

Lewis-Acid-Mediated Intramolecular Trifluoromethylthiolation of Alkenes with Phenols: Access to SCF3-Containing Chromane and Dihydrobenzofuran Compounds.

A Lewis-acid-mediated intramolecular trifluoromethylthiolation of alkenes with phenols that can offer direct access to SCF3-containing chromane and dihydrobenzofuran compounds was disclosed for the first time. Numerous SCF3-containing chromanes were obtained in moderate to good yields using γ-substituted 2-allyphenols as substrates. Meanwhile, various SCF3-containing dihydrobenzofurans with oxa-quaternary centers were also delivered in moderate to good yields using ß-substituted 2-allyphenols as substrates.

Coumarin derivatives with anticancer activities: An update.

Cancer can invade or spread to almost all parts of the body. The increasing morbidity and high mortality of cancer create a great demand for the development of novel anticancer drugs. Coumarin derivatives are ubiquitous in nature and can readily interact with diverse enzymes and receptors in cancer cells via weak bond interactions; hence, coumarin is a highly privileged pharmacophore for the development of novel anticancer agents. This review will focus on the recent development of coumarin hybrids as potential anticancer agents covering articles published from 2019 to 2020.

Lewis-Acid-Mediated Thiocyano Semipinacol Rearrangement of Allylic Alcohols for Construction of α-Quaternary Center ß-Thiocyano Carbonyls.

An electrophilic thiocyano semipinacol rearrangement of allylic alcohols has been achieved for the first time by using N-thiocyano-dibenzenesulfonimide (NTSI). This approach provides a direct, simple, and efficient strategy for the formation of thiocyano carbonyl compounds with moderate to excellent yields. Meanwhile, an all-carbon quaternary center was rapidly constructed. In addition, an asymmetric version of this tandem reaction was preliminarily investigated.

Lewis Base/Brønsted Acid Co-Catalyzed Asymmetric Thiolation of Alkenes with Acid-Controlled Divergent Regioselectivity.

A divergent strategy for the facile preparation of various enantioenriched phenylthio-substituted lactones was developed based on Lewis base/Brønsted acid co-catalyzed thiolation of homoallylic acids. The acid-controlled regiodivergent cyclization (6-endo vs. 5-exo) and acid-mediated stereoselective rearrangement of phenylthio-substituted lactones were explored. Experimental and computational studies were performed to clarify the origins of the regioselectivity and enantioselectivity. The calculation results suggest that C-O and C-S bond formation might occur simultaneously, without formation of a commonly supposed catalyst-coordinated thiiranium ion intermediate and the potential π-π stacking between substrate and SPh as an important factor in the enantio-determining step. Finally, this methodology was applied in the rapid syntheses of the bioactive natural products (+)-ricciocarpin A and (R)-dodecan-4-olide.

Lewis base-catalyzed asymmetric sulfenylation of alkenes: construction of sulfenylated lactones and application to the formal syntheses of (-)-nicotlactone B and (-)-galbacin.

An efficient method for the preparation of chiral sulfenylated lactones has been described based on Lewis base-catalyzed enantioselective sulfenylation of unsaturated carboxylic acids. The scope of this method includes two enantioselective cyclization reactions: 5-endo and 6-exo thiolactonizations of alkenes. Two types of lactones were obtained with up to 95% ee and 99% yield. Additionally, this methodology has been applied in the formal syntheses of bioactive natural products (-)-nicotlactone B and (-)-galbacin.

TMSCl-Catalyzed Electrophilic Thiocyano Oxyfunctionalization of Alkenes Using N-Thiocyano-dibenzenesulfonimide.

Numerous electrophilic thiocyano oxyfunctionalization reactions of alkenes have been achieved using N-thiocyano-dibenzenesulfonimide, which is a new electrophilic thiocyanation reagent and could be easily prepared in two steps from dibenzenesulfonimide. This approach provides efficient, simple, and modular methods for the formation of SCN-containing heterocycles such as lactones, tetrahydrofurans, dihydrofurans, and dihydrobenzofurans in moderate to excellent yields. Meanwhile, diverse oxa-quaternary centers were rapidly constructed. Additionally, this protocol is free of transition metals and features broad substrate toleraance and mild reaction conditions.

Recent advances of pyrazole-containing derivatives as anti-tubercular agents.

One-third of the world's population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles. Numerous of pyrazole-containing derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency and may have novel mechanism of action. This review aims to outline the recent achievements in pyrazole-containing derivatives as anti-TB agents and their structure-activity relationship.

Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids.

A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12µg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5µg/mL) than the parent gatifloxacin (GTFX) (CC50: 125µg/mL). Among them, 61 (MIC: 0.025µg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05µg/mL), GTFX (MIC: 0.78µg/mL) and RIF (MIC: 0.39µg/mL) against MTB H37Rv. The most active conjugate 6k (MIC: 0.06µg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128µg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.

Azide-alkyne cycloaddition towards 1H-1,2,3-triazole-tethered gatifloxacin and isatin conjugates: Design, synthesis and in vitro anti-mycobacterial evaluation.

Twelve novel 1H-1,2,3-triazole-tethered gatifloxacin (GTFX) isatin conjugates 5a-l with greater lipophilicity compared with GTFX were designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The preliminary results showed that all the targets (MIC: 0.10-8 µg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but eight of them (CC50: 7.8-62.5 µg/mL) were much more toxic than the parent GTFX (CC50: 125 µg/mL). Among them, 5g (MIC: 0.10 µg/mL) was 4-8 times more potent in vitro than the references GTFX (MIC: 0.78 µg/mL) and RIF (MIC: 0.39 µg/mL) against MTB H37Rv, but less active than INH (MIC: 0.05 µg/mL). The most potent 5g and 5h (MIC: 0.25 µg/mL) were 4->512 times more active than the three references (MIC: 1.0->128 µg/mL) against MDR-TB. Unfortunately, both of the two hybrids (CC50: 7.8 µg/mL) were much more cytotoxic than the other derivatives, need to be further optimized.

Synthesis, characterization and spectral properties of substituted tetraphenylporphyrin iron chloride complexes.

A series of substituted tetraphenylporphyrin iron chloride complexes [RTPPFe(III)Cl, R=o/p-NO2, o/p-Cl, H, o/p-CH3, o/p-OCH3] were synthesized by a novel universal mixed-solvent method and the spectral properties of free base porphyrins and iron porphyrin compounds were compared with each other. The experimental results showed that the one-pot mixed solvent method was superior to the two-step method in the yields, reaction time and workup of reaction mixtures for the synthesis of iron porphyrin compounds. The highest yields (28.7%-40.4%) of RTPPFe(III)Cl were obtained in the mixed solvents propionic acid, glacial acetic acid and m-nitrotoluene under reflux for 2 h. A detailed analysis of ultraviolet-visible (UV-vis), infrared (IR) and far-infrared (FIR) spectra suggested the transformation from free base porphyrins to iron porphyrins. The red shift of the Soret band in ultraviolet-visible spectra due to the presence of p-nitrophenyl substituents and the blue shift of Fe-Cl bond of TPPFeCl in far-infrared spectra were further explained by the electron transfer and molecular planarity in the porphyrin ring.

[Identification of Fructus Schisandrae chinensis and Fructus Schisandrae sphenantherae in wu zi yan zong pill by RP-HPLC analysis].

OBJECTIVE: To identify Fructus schisandrae chinensis and Fructus schisandrae sphenantherae in wu zi yan zong pill (WZYZP). METHODS: Columm SUPELCOSIL C18; Mobile phase: methanol-water (65:35); Detection wavelength: 254 nm. RESULTS: Using above optimum chromatography conditions, the HPLC chromatography of relative medicinal materials and WZYZP was established. CONCLUSION: HPLC chromatography can be used for identification of Fructus schisandrae chinensis and Fructus schisandrae sphenantherae in WZYZP.