Glycoconjugates of adefovir and tenofovir as asialoglycoprotein-mediated Anti-HBV prodrugs with enhanced liver targeting.

Hepatitis B virus (HBV) infection remains a significant global health challenge, often leading to severe liver complications such as cirrhosis and cancer. Current treatments rely heavily on nucleos(t)ide analogues like adefovir and tenofovir due to their potent antiviral effects. However, their clinical utility is limited by insufficient liver targeting, leading to off-target side effects, particularly nephrotoxicity.

Discovery of a potent anticancer agent against pancreatic ductal adenocarcinoma targeting FAK with DFG-out state and JAK/Aurora kinases.

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer because of the difficulty in diagnosis and its resistance to chemotherapy. Focal adhesion kinase (FAK) is found overexpressed in PDAC, and targeting FAK has been proved to impede the progress of PDAC. However, most of FAK inhibitors were reported to bind with FAK in a DFG-in conformation, leading to a limited anti-tumor effect in clinical studies.

Scutellarein derivatives with histamine H receptor antagonism and cholinesterase inhibitory potency as multi target-directed ligands for possible Alzheimer's disease therapy.

A series of scutellarein 7--amino acid carbamate-4'-cycloalkylamine propyl ether conjugates were designed and synthesized for the first time as multifunctional agents for Alzheimer's disease (AD) therapy. The designed compounds exhibited more balanced and effective multi-target potency. Among them, compound 11l, -Valine carbamate derivative of scutellarein cycloheptylamine ether, exhibited the most potent inhibition of electric eel AChE enzymes and human AChE enzymes, with an IC values of 7.

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.

Integrase plays an important role in the life cycle of HIV-1, and integrase strand transfer inhibitors (INSTIs) can effectively impair the viral replication. However, drug resistance mutations have been confirmed to decrease the efficacy of INSTI during the antiviral therapy. Herein, indole-2-carboxylic acid (1) was found to inhibit the strand transfer of integrase, and the indole nucleus of compound 1 was observed to chelate with two Mg ions within the active site of integrase.

Rh(III)-Catalyzed C7-Alkylation of Isatogens with Malonic Acid Diazoesters.

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one -oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the -oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the -oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

The Discovery of Indole-2-carboxylic Acid Derivatives as Novel HIV-1 Integrase Strand Transfer Inhibitors.

As an important antiviral target, HIV-1 integrase plays a key role in the viral life cycle, and five integrase strand transfer inhibitors (INSTIs) have been approved for the treatment of HIV-1 infections so far. However, similar to other clinically used antiviral drugs, resistance-causing mutations have appeared, which have impaired the efficacy of INSTIs. In the current study, to identify novel integrase inhibitors, a set of molecular docking-based virtual screenings were performed, and indole-2-carboxylic acid was developed as a potent INSTI scaffold.

Effects of a Nanonetwork-Structured Soil Conditioner on Microbial Community Structure.

Fertilizer application can increase yields, but nutrient runoff may cause environmental pollution and affect soil quality. A network-structured nanocomposite used as a soil conditioner is beneficial to crops and soil. However, the relationship between the soil conditioner and soil microbes is unclear.

Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease.

Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC values of 6.

Synthesis of diarylmethyl thioethers a DABCO-catalyzed 1,6-conjugate addition reaction of -quinone methides with organosulfur reagents.

A rapid and simple method was developed for the synthesis of diarylmethyl thioethers a DABCO-catalyzed 1,6-conjugate addition reaction of -quinone methides (-QMs) with organosulfur reagents. A series of diarylmethyl thioethers were synthesized at 13-85% yields by this method. After that, the antibacterial activities of synthesized diarylmethyl thioethers and their derivatives were evaluated.

Protecting-Group-Free Synthesis of Meridianin A-G and Derivatives and Its Antibiofilm Evaluation.

Herein, a protecting-group-free protocol was developed to realize a time and step economy diversification of the Meridianin alkaloid. A broad range of substituents are tolerated to deliver the products in moderate to high yields, and the first synthesis of Meridianin B was achieved. The simplicity of this protocol enables the rapid construction of a Meridianin derivative library for antibiofilm evaluation.

DBU-Catalyzed Aerobic CDC Reaction of Thiophenols.

A convenient method was developed for the preparation of thiolated compounds a DBU-catalyzed aerobic cross-dehydrogenative coupling (CDC) reaction. The established protocol is environmentally friendly and operationally simple. Substrates like (hetero)aryl acetates, (hetero)aryl ketones, and indoles could be transformed into the corresponding thiolated products in moderate to high yields and further applied in the preparation of bioactive compounds in a prefunctionalization-free manner.

Synthesis and antibiofilm evaluation of N-acyl-2-aminopyrimidine derivatives against Acinetobacter baumannii.

The overuse of antibiotics will led to the increase of drug resistance. Especially, the multidrug-resistant A. baumannii became the leading cause of nosocomial infections with high rates of morbimortality.

Synthesis and antibacterial activity studies of indirubin-3'-monoximes.

Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities.

Transcriptome Analysis of Tryptophan-Induced Resistance against Potato Common Scab.

Potato common scab (CS) is a worldwide soil-borne disease that severely reduces tuber quality and market value. We observed that foliar application of tryptophan (Trp) could induce resistance against CS. However, the mechanism of Trp as an inducer to trigger host immune responses is still unclear.

Design, Synthesis, and Biological Evaluation of N14-Amino Acid-Substituted Tetrandrine Derivatives as Potential Antitumor Agents against Human Colorectal Cancer.

As a typical dibenzylisoquinoline alkaloid, tetrandrine (TET) is clinically used for the treatment of silicosis, inflammatory pulmonary, and cardiovascular diseases in China. Recent investigations have demonstrated the outstanding anticancer activity of this structure, but its poor aqueous solubility severely restricts its further development. Herein, a series of its 14--amino acid-substituted derivatives with improved anticancer effects and aqueous solubility were designed and synthesized.

Role of no table salt on hypertension and stroke based on large sample size from National Health and Nutrition Examination Survey database.

Background: To assess the associations between no table salt and hypertension or stroke.

Methods: The data of 15,352 subjects were collected from National Health and Nutrition Examination Survey (NHANES) database. All subjects were divided into no hypertension or stroke group (n = 10,894), hypertension group (n = 5888), stroke group (n = 164) and hypertension and stroke group (n = 511).

A solid-supported organocatalyst for asymmetric Mannich reaction to construct C2-quaternary indolin-3-ones.

A simple and novel solid-supported organocatalyst from a 2-chlorotrityl chloride resin-immobilized 4-hydroxyproline was developed, and this organocatalyst has been used for the asymmetric Mannich reaction of 2-aryl-3-indol-3-ones and aldehydes/ketones. A series of C2-quaternary indolin-3-ones were prepared in good yields (up to 83%) and with excellent diastereoselectivities (up to 20 : 1) and enantioselectivities (up to 99% ee). In addition, the organocatalyst can be recovered by simple filtration and also be reused for the asymmetric Mannich reaction without significant loss of catalytic efficiency.

Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease.

In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC values of 6.01 ± 1.

Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6.

Histone deacetylase 6 (HDAC6) is a potential therapeutic target for treating several diseases. A recent study revealed that HDAC6 is important for NLRP3 inflammasome activation, suggesting that targeting HDAC6 could be useful for treating many inflammatory disorders. Using the proteolysis targeting chimera (PROTAC) strategy, we herein report an HDAC6 degrader with low cytotoxicity by tethering a selective HDAC6 inhibitor derived from a natural product, indirubin, with pomalidomide, a CRBN E3 ligand.

iTRAQ-Based Proteomics Analysis of Response to Leaves Treated with the Plant Phytotoxin Thaxtomin A.

Thaxtomin A (TA) is a phytotoxin secreted by that causes common scab in potatoes. However, the mechanism of potato proteomic changes in response to TA is barely known. In this study, the proteomic changes in potato leaves treated with TA were determined using the Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique.

Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer.

To utilize the unique scaffold of a natural product indirubin, we herein adopted the strategy of combined pharmacophores to design and synthesize a series of novel indirubin derivatives as dual inhibitors against cyclin-dependent kinase (CDK) and histone deacetylase (HDAC). Among them, the lead compound with remarkable CDK2/4/6 and HDAC6 inhibitory activity of IC = 60.9 ± 2.

Cysteine derivatives as acetyl lysine mimics to inhibit zinc-dependent histone deacetylases for treating cancer.

Zinc-dependent histone deacetylases (HDACs) are important epigenetic regulators that have become important drug targets for treating cancer. Although five HDAC inhibitors have been approved for treating several cancers, there is still a huge demand on discovering new HDAC inhibitors to explore the therapeutic potentials for treating solid tumor cancers. Substrate mimics are a powerful rational design approach for the development of potent inhibitors.