Alstomaphylines A-K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity.

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Bis-piperidine alkaloids from the peels of Areca catechu.

Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.

Total Synthesis of Quebrachamine and Kopsiyunnanine D.

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

Silver/Antimony-Base Multifunctional Double Perovskite with H/F Substitution Enhance Properties.

Two-dimensional double perovskites have experienced rapid development due to their outstanding optoelectronic properties and diverse structural characteristics. However, the synthesis of high-performance multifunctional compounds and the regulation of their properties still lack relevant examples. Herein, we synthesized two multifunctional compounds, (C6H14N)4AgSbBr8 (1) and (F2-C6H12N)4AgSbBr8 (2), which exhibit high solid-state phase transition temperature, bistable dielectric constant switching, second harmonic generation (SHG), and bright emission. Through H/F substitution, the transition temperature increases and achieves a smaller band gap attributed to reduced interlayer spacing. Furthermore, we investigated the broad emission mechanism of the compounds through first-principles calculation and variable-temperature fluorescence, confirming the presence of the STE1 emission. Our work provides insight into the further development of multifunctional compounds and chemical modification that enhances compound properties.

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells.

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 µM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.