Synthesis, in vitro Α-Glucosidase, and acetylcholinesterase inhibitory activities of novel Indol-Fused Pyrano[2,3-D]Pyrimidine compounds.

In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.

Multiple Transcriptomic Analyses Explore Potential Synaptic Biomarker Rabphilin-3A for Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD.

Synthesis of new DOPO derivatives and investigation of their synergistic effect with APP-PEI on the flame retardancy of epoxy composite.

Epoxy resin has been extensively used in many industrial and daily applications due to its unique properties. However, the high flammability of epoxy has limited its further development. DOPO derivatives, which are organophosphorus compounds, are highly effective components of flame retardant epoxy composites due to their good compatibility with the resin and their lower toxicity compared to halogenated compounds. This study synthesized sixteen new DOPO derivatives, characterizing their chemical structures with NMR spectroscopy. The combination of synthesized DOPO derivatives and APP-PEI (ammonium polyphosphate-polyethyleneimine) has shown a synergistic effect on enhancing the flame retardancy of epoxy resin with the UL-94 V-0 rating and the LOI value of 28.6%. Moreover, the epoxy composites displayed relatively high mechanical performance with the impact strength of 26-28 kJ m-2.

Are ß-H eliminations or alkene insertions feasible elementary steps in catalytic cycles involving gold(I) alkyl species or gold(I) hydrides?

The ß-H-elimination in the (iPr)AuEt complex and its microscopic reverse, the insertion of ethene into (iPr)AuH, were investigated in a combined experimental and computational study. Our DFT-D3 calculations predict free-energy barriers of 49.7 and 36.4 kcal mol(-1) for the elimination and insertion process, respectively, which permit an estimation of the rate constants for these reactions according to classical transition-state theory. The elimination/insertion pathway is found to involve a high-energy ethene hydride species and is not significantly affected by continuum solvent effects. The high barriers found in the theoretical study were then confirmed experimentally by measuring decomposition temperatures for several different (iPr)Au(I) -alkyl complexes which, with a slow decomposition at 180 °C, are significantly higher than those of other transition-metal alkyl complexes. In addition, at the same temperature, the decomposition of (iPr)AuPh and (iPr)AuMe, both of which cannot undergo ß-H-elimination, indicates that the pathway for the observed decomposition at 180 °C is not a ß-H-elimination. According to the calculations, the latter should not occur at temperatures below 200 °C. The microscopic reverse of the ß-H-elimination, the insertion of ethene into the (iPr)AuH could neither be observed at pressures up to 8 bar at RT nor at 1 bar at 80 °C. The same is true for the strain-activated norbornene.

Cu-catalyzed Synthesis of Quinolines by Dehydrogenative Reaction of 2-Aminobenzyl Alcohol and Ketones: A Combined Experimental and Computational Study.

Quinoline derivatives are important moieties in bioactive molecules and advanced materials. However, an efficient strategy to synthesize quinoline derivatives remains challenging. Herein, we describe an efficient and practical method for the synthesis of quinolines by Cu-catalyzed cyclization of 2-amino benzyl alcohol with ketones (or secondary alcohols) via an acceptorless dehydrogenation pathway. Interestingly, a range of highly functionalized quinolines is prepared in good yields using low catalyst loading under relatively mild conditions. Furthermore, density functional theory (DFT) calculations are carried out to investigate mechanistic insights for the acceptorless dehydrogenation pathway.

In vivo anticancer activity of maesopsin 4-O-ß-glucoside isolated from leaves of Artocarpus tonkinensis A. Chev. Ex Gagnep.

OBJECTIVE: To investigate the antitumor effect of maesopsin 4-O-ß-glucoside (TAT2) isolated from the leaves of Artocarpus tonkinensis (A. tonkinensis) A. Chev. ex Gagnep. METHODS: The antitumor activity of TAT2 was evaluated in Lewis lung carcinoma (LLC) tumor-bearing mice. BALB/c mice had tumors induced by implantation with 2 × 10(6) LLC cells into the subcutaneous right posterior flank. Tumor-bearing mice were treated orally with a range of doses of TAT2 and a standard drug, doxorubicin. Animals were observed for tumor growth and mortality rate. Blood was collected to determine hematological and biochemical parameters. RESULTS: TAT2 was isolated from an ethanolic extract of A. tonkinensis leaves. Its structure was determined by MS and NMR spectroscopy, and identified as TAT2. The compound did not show acute toxicity at the highest dose tested (2000 mg/kg body weight). TAT2 exhibited antitumor activity by decreasing tumor growth, increasing the survival rate, and ameliorating some hematological and biochemical parameters at doses of 100 and 200 mg/kg body weight (P < 0.05). CONCLUSIONS: These results indicate that TAT2 possesses clear antitumor activity. Due to its bioavailability and low toxicity, and the fact that it could be isolated in a large scale from A. tonkinensis leaves, the compound shows promise as a potential anticancer drug.