Deciphering roles of protein post-translational modifications in IgA nephropathy progression and potential therapy.

Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both genetics and epigenetics play a pivotal role in the occurrence and progression of IgAN. Post-translational modification (PTM) has been revealed to critically participate in IgAN development and progression because PTM dysregulation results in impaired degradation of proteins that regulate IgAN pathogenesis. A growing number of studies identify that PTMs, including sialylation, o-glycosylation, galactosylation, phosphorylation, ubiquitination and deubiquitination, modulate the initiation and progression of IgAN. Hence, in this review, we discuss the functions and mechanisms of PTMs in regulation of IgAN. Moreover, we outline numerous compounds that govern PTMs and attenuate IgAN progression. Targeting PTMs might be a useful strategy to ameliorate IgAN.

Copper-Catalyzed Nitrogen Atom Transfer to Isoquinolines via C-N Triple Bond Cleavage and Three-Component Cyclization.

A copper(I)-catalyzed tandem reaction of 2-bromoaryl ketones, terminal alkynes, and CH3CN is developed, which combines N atom transfer and three-component [3 + 2 + 1] cyclization, and efficiently produces densely functionalized isoquinolines in a facile, highly selective, and general manner. In the reaction, the formation of aromatic C-N bonds along with the complete C-N triple bond cleavage is first realized; Cu(III)-acetylide species might serve as the intermediates, which allow highly selective 6-endo-dig cyclization.

Copper-Catalyzed 6-endo-dig Cyclization-Coupling of 2-Bromoaryl Ketones and Terminal Alkynes toward Naphthyl Aryl Ethers in Water.

The cyclization-coupling reaction of 2-bromoaryl ketones and terminal alkynes is first realized by copper catalysis, which produces polyfunctional naphthyl aryl ethers in moderate to excellent yields with broad substrate scope and good functional group tolerance. This reaction proceeds via 6-endo-dig cyclization and C(sp2)-O coupling using green H2O as the unique solvent and 5-bromopyrimidin-2-amine as the critical additive. Mechanistically, a unique Cu(III)-acetylide probably is the key intermediate, which allows exclusive 6-endo-dig selectivity.

SARS-CoV-2: The Monster Causes COVID-19.

Coronaviruses are viruses whose particles look like crowns. SARS-CoV-2 is the seventh member of the human coronavirus family to cause COVID-19 which is regarded as a once-in-a-century pandemic worldwide. It holds has the characteristics of a pandemic, which has broy -55ught many serious negative impacts to human beings. It may take time for humans to fight the pandemic. In addition to humans, SARS-CoV-2 also infects animals such as cats. This review introduces the origins, structures, pathogenic mechanisms, characteristics of transmission, detection and diagnosis, evolution and variation of SARS-CoV-2. We summarized the clinical characteristics, the strategies for treatment and prevention of COVID-19, and analyzed the problems and challenges we face.

The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges.

Lung cancer is one of the common malignant tumors that threaten human life with serious incidence and high mortality. According to the histopathological characteristics, lung cancer is mainly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for about 80-85% of lung cancers. In fact, lung cancer metastasis is a major cause of treatment failure in clinical patients. The underlying reason is that the mechanisms of lung cancer metastasis are still not fully understood. The metastasis of lung cancer cells is controlled by many factors, including the interaction of various components in the lung cancer microenvironment, epithelial-mesenchymal transition (EMT) transformation, and metastasis of cancer cells through blood vessels and lymphatics. The molecular relationships are even more intricate. Further study on the mechanisms of lung cancer metastasis and in search of effective therapeutic targets can bring more reference directions for clinical drug research and development. This paper focuses on the factors affecting lung cancer metastasis and connects with related molecular mechanisms of the lung cancer metastasis and mechanisms of lung cancer to specific organs, which mainly reviews the latest research progress of NSCLC metastasis. Besides, in this paper, experimental models of lung cancer and metastasis, mechanisms in SCLC transfer and the challenges about clinical management of lung cancer are also discussed. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients.

Cu(i) catalysis for selective condensation/bicycloaromatization of two different arylalkynes: direct and general construction of functionalized C-N axial biaryl compounds.

Selective condensation/bicycloaromatization of two different arylalkynes is firstly developed under ligand-free copper(i)-catalysis, which allows the direct synthesis of C-N axial biaryl compounds in high yields with excellent selectivity and functional group tolerance. Due to the critical effects of Cu(i) catalyst and HFIP, many easily occurring undesired reactions are suppressed, and the coupled five-six aromatic rings are constructed via the selective formation of two C(sp2)-N(sp2) bonds and four C(sp2)-C(sp2) bonds. The achievement of moderate enantioselectivity verifies its potential for the simplest asymmetric synthesis of atropoisomeric biaryls. Western blotting demonstrated that the newly developed compounds are promising targets in biology and pharmaceuticals. This unique reaction can construct structurally diverse C-N axial biaryl compounds that have never been reported by other methods, and might be extended to various applications in materials, chemistry, biology, and pharmaceuticals.

Cu-Catalyzed Oxidative Thioesterification of Aroylhydrazides with Disulfides.

An alternative thioesterification reaction via copper-catalyzed oxidative coupling of readily available aroylhydrazides with disulfides is developed, in which oxidative expulsion of N2 overcomes the activation barrier between the carboxylic acid derivatives and the products. The reaction produces various thioesters in good to excellent yields with good functional group tolerance. In the reaction, stable and easily available aroylhydrazides are used as acyl sources and the relatively odorless disulfides are used as S sources. Mechanistic investigations demonstrate that the reaction of copper salt and oxidant (NH4)2S2O8 allows for achievement of tandem processes, including deprotonation, free-radical-mediated denitrogenation, and C-S bond formation.

A review: Natural polysaccharides from medicinal plants and microorganisms and their anti-herpetic mechanism.

The infections caused by Herpes simplex viruses (HSV-1 and -2) are seriously endangering the health of all human beings. Once infected with these two viruses, it will cause life-long latency in the host, and the continuous recurrence of the infection will seriously affect the quality of life. Moreover, infections with HSV-1 and HSV-2 have been reported to make the body susceptible to other diseases, such as Alzheimer's disease and HIV. Thus, more attention should be paid to the development of novel anti-HSV drugs. Polysaccharides obtained from medicinal plants and microorganism (both land and sea) are reported to be promising anti-herpes substances. However, their antiviral mechanisms are complex and diverse, which includes direct inhibition of virus life cycle (Adsorption, penetration, genetic material and protein synthesis) and indirectly through improving the body's immunity. And each step of the research processes from extraction to structural analysis contributes to the result in terms of antiviral activity. Therefore, The complex mechanisms involved in the treatment of Herpes simplex infections makes development of new antiviral compounds is difficult. In this paper, the mechanisms of polysaccharides in the treatment of Herpes simplex infections, the research processes of polysaccharides and their potential clinical applications were reviewed.

Correction: Recent advances in the direct ß-C(sp2)-H functionalization of enamides.

Correction for 'Recent advances in the direct ß-C(sp2)-H functionalization of enamides' by Tonghao Zhu et al., Org. Biomol. Chem., 2020, DOI: 10.1039/c9ob02649e.

Ixeris sonchifolia: a review of its traditional uses, chemical constituents, pharmacology and modern applications.

Ixeris sonchifolia (IS), principally its dried form, is widely used as traditional and folk medicines in some Asian countries, especially China. In this review, we summarized its traditional uses, chemical constituents, quality control measures, pharmacological activities, therapeutic evaluation, toxicity evaluation and clinical applications. 130 chemical constituents isolated from IS have been reported, including flavones, sesquiterpenes, triterpenes, phenylpropanoids, organic acids and others. They showed various pharmacological activities, such as protecting cardiocerebral vascular system, anticancer effect and antiviral etc. The quality control evaluation studies, clinical applications, other possible applications and suggestions for future research also were discussed. The aim of this review is to critically appraise the available literature and suggest directions for further development of IS to improve its medical value and use.

Recent advances in the direct ß-C(sp2)-H functionalization of enamides.

The direct ß-C(sp2)-H functionalization of enamides has attracted increasing attention among the chemical community, due to the diverse biological and pharmaceutical activities of enamides. This review is focused on the recent advances in the direct ß-C(sp2)-H functionalization of enamides, mainly including arylation, alkenylation, alkynylation, alkylation, acylation, sulfonylation, phosphorylation, and others. Additionally, mechanistic features of these transformations are also discussed.

Salvia plebeia R. Br. : an overview about its traditional uses, chemical constituents, pharmacology and modern applications.

Salvia plebeia R. Br. (SP), has been widely used in traditional Chinese medicine (TCM). It contains a number of chemical components and reported to possess a variety of pharmacological activities. SP is distributed in many countries such as China, Korea, Japan, Afghanistan and India. SP was first described in Compendium of Materia Medica in the Ming dynasty. The aim of this review is to compile all the information reported in the literature on SP. This review covers traditional uses, including 16 TCM classics and 21 traditional prescriptions; a total of 93 compounds from SP have been reported, including flavonoids, monoterpenoids, sesquiterpenoids, diterpenoids, triterpenes, phenolic acids etc; biological actives such as antioxidant, antimicrobial, hypoglycaemic, anti-inflammatory, analgesic, sedative, antiasthmatic, antiviral, antitumour, hepatoprotective effects etc. In addition, this paper also compiled the quality control studies and clinical applications. The future prospects and the existing problems of SP were also discussed. Overall, we believe this review will be a comprehensive record of SP for researchers to refer for carrying out for further research.

Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer.

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.

Cu(I)-Catalyzed 6- endo-dig Cyclization of Terminal Alkynes, 2-Bromoaryl Ketones, and Amides toward 1-Naphthylamines: Applications and Photophysical Properties.

Functional group substituted 1-naphthylamines, especially N-methylated ones, play important roles in numerous chemical and biological processes. However, these compounds' general and step-economic syntheses are highly limited, which seriously restricts efforts to improve the properties and develop new functions for this kind of compound. In this report, we describe the development of an efficient, convenient, and general method for the synthesis of valuable functionalized 1-naphthylamines directly from readily available terminal alkynes, 2-bromoaryl ketones, and amides via Cu(I)-catalyzed benzannulation in a green solvent (i.e., water) under Pd- and ligand-free conditions. A total of 82 functionalized 1-naphthylamines, especially synthetically and biologically useful N-methylated compounds, are synthesized in isolated yields up to 95%. Some unique features of the reaction are as follows: (1) exclusive 6 -endo-dig selectivity, (2) ready incorporation of a broad range of functional groups directly from easily available substrates, and (3) amides that can be used as aminating agents and that are excellent alternatives to toxic and/or odorous amines. Due to facile tuning of functional groups for the reaction, the products possess good electronic donor-acceptor structures and exhibit intriguing photophysical properties, such as tunable and polarity-sensitive fluorescence emission and large Stokes shifts (up to 258 nm). Utilizing the products' unique polarity-sensitive fluorescence response, we successfully applied the 1-naphthylamine derivatives, such as compound 91, to image lipid droplets (LDs) and monitor cellular LDs growth. The previously mentioned advantages of this methodology, along with the mild conditions, simple operation, and scalable synthesis, may allow this novel reaction to be extended to varied applications in chemistry, biology, and materials science.

Synthesis and biological evaluation of kojic acid derivatives containing 1,2,4-triazole as potent tyrosinase inhibitors.

A series of 5-substituted-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole derivatives were synthesized by nucleophilic substitution reaction of 5-hydroxy-2-chloromethyl -4H-pyran-4-one with 5-substituted-3-mercapto-4-amino-1,2,4-triazole, and their inhibitory effects on mushroom tyrosinase were evaluated. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity. Specifically, 5-(4-chlorophenyl)-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole (6j) exhibited the most potent tyrosinase inhibitory activity with IC50 value of 4.50 ± 0.34 µm. The kinetic studies of the compound (6j) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was also discussed.

Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.

A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed.