Discovery and development of tricyclic matrinic derivatives as anti-diabetic candidates by AMPKα activation

Evolution and Discovery of Matrine Derivatives as a New Class of Anti-Hepatic Fibrosis Agents Targeting Ewing Sarcoma Breakpoint Region 1 (EWSR1)

“…First, the benzeneaminoformylmethyl motif, as an active group, was retained at 12 N -position, and 11-butanol was replaced by butane with higher pharmacokinetic stability, − by which compounds 7a–d were generated. Compound 7a gave comparable activity to lead 1 , while compounds 7b–d gave elevated activity compared to lead 1 .…”

“…Using the procedures reported previously, intermediate 5 was prepared following a five-step procedure including t -butyloxycarbonyl (Boc) protection on the 12N atom, ester reduction, hydroxyl sulfonylation with tosyl (Ts), reductive-elimination of OTs, and deprotection of Boc in a good yield. − The nucleophilic substitution reaction between 5 and substituted isocyanates or aminoformyl methyl bromides achieved products 6a – n and 7a – h in 30–78% yields. The nucleophilic substitution reaction between 2 and substituted isocyanates led to methyl 12 N- aminoformyl matrinates ( 8a and 8b ) in 65–78% yields, which underwent a reduction reaction via LiAlH 4 to afford the products 9a and 9b in high yields .…”

“…Multiple matrine analogues with a diversity of structures disclosed reasonable to appealing antifibrosis activity; however, they were optimized on the basis of the four-ring scaffold. Our team initiated the antifibrosis activity study on a new tricyclic matrine scaffold, with the advantages of a simplified structure as well as a higher druglike profile. − Therefore, we presented a potent matrinic scaffold for antifibrosis application.…”

Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1

“…Both AMP and ATP were detected by commercial kits on the basis of bioluminescence assay, as described previously ( Li et al, 2023 ). After BBR treatment, cells were lysed and reaction was started with prepared reagents according to the manufactures’ protocols.…”

Fluorometric and colorimetric dual-mode sensing of α-glucosidase based on aggregation-induced emission enhancement of AuNCs

“…Diabetes, as a metabolic and endocrine disease, has severely threatened human health on account of its high morbidity. [1][2][3] It is reported that almost 500 million people are suffering from diabetes or prediabetes, and the influenced population is constantly expanding. 4 Significantly, due to the disturbance of the metabolism triggered by diabetes, diabetic patients are always tortured by many complications including kidney diseases, coronary heart disease, cerebrovascular disease, etc.…”