Journal of Natural Products 最新文献

In the search for novel natural products with hepatoprotective effects against acetaminophen-induced acute liver injury, the marine-derived fungus Aspergillus aculeatinus WHUF0198 was investigated. Seventeen undescribed pyranopyridone alkaloids, aculeapyridones A–Q (1–17), were isolated by bioactivity-guided fractionation of an extract obtained by coculture of the A. aculeatinus WHUF0198 with the mangrove-associated fungus Penicillium sp. DM27. Notably, compounds 12–15, which possessed a unique N-methoxy group, were identified as activation products of fungal coculture in liquid media. The structures and absolute configurations of these compounds were elucidated using a combination of universal spectroscopic techniques (NMR and HR-ESI-MS), ECD calculations, and single crystal X-ray diffraction analysis. All the isolated compounds, except 8 and 17, were evaluated for their hepatoprotective activity against acetaminophen-induced acute liver injury in vitro. Compounds 1–7, 9, 10 and 12–15 increased cell viability and reduced alanine aminotransferase (ALT) levels of acetaminophen-induced murine hepatocytes at either 5 or 10 μM.

As a continuation of our pharmacognostic studies on different Glycyrrhiza species growing in Türkiye, the phytochemical investigation of the roots of Glycyrrhiza asymmetrica Hub.-Mor., a licorice species endemic to Türkiye, was carried out. This study yielded twenty-three secondary metabolites (1–23) including nine previously unreported compounds: two dihydroaurone-3-enoic acids, licoaurone A (1) and licoaurone B (2), isoflavan hydroxypreglabridin (3), isoflavanone cyclodeoxykievitone (4), flavanone-3-ol glycyasymmetrol (5), and four bi-isoflavans, glycyasymmetrica A–D (6–9). The structures of isolated compounds were established by NMR and MS experiments. The relative configurations (6–9) were assigned by a combined quantum mechanical/NMR approach, comparing the experimental ¹³C/¹H NMR chemical shift data and the related predicted values. The absolute configurations of compounds 1–9 were assigned by comparison of their experimental electronic circular dichroism curves with the TDDFT-predicted curves. All isolated compounds were also evaluated for their cytotoxic activity against MCF-7, HeLa, HepG2, and A549 cancer cell lines by using MTT assay.

Phospholipids are an essential constituent of cells with all life thought to produce these compounds with either a glycerol or sphingoid moiety at their core. For the first time, we demonstrate that a thermophilic bacterium, Limisphaera ngatamarikiensis NGM72.4^T, produces a third type of phospholipid, serinophospholipids, which are distinct from glycero- and sphingophospholipids by featuring a serinol backbone instead. We show that the major serinophospholipid metabolites are N,O-diacylserinophospho-N-methylethanolamine and N,O-diacylserinophosphoethanolamine, and that serinophospholipids constitute up to 38% of the phospholipid mass. Furthermore, we demonstrate that these metabolites are further differentiated from “traditional” bacterial glycerophospholipids by their backbone configuration. In contrast to bacterial glycerophospholipids, which have an sn-glycerol-3-phosphate (G3P) architecture, the newly discovered serinophospholipids have an (S)-configured serinol core that is equivalent to the sn-glycerol-1-phosphate (G1P) arrangement characteristic of Archaea.

Six new aurovertins (1–6) and a new citreoviridin derivative (7), together with six known analogues (8–13), were isolated from the marine-derived Penicillium sp. OUCMDZ-5930. Their structures were determined based on detailed spectroscopic analysis and ECD calculations. The putative nonenzymatic formation from citreoviridin to various aurovertins was presented, which was confirmed by chemical transformations. These results provide new insights into the formation mechanism of the 2,6-dioxabicyclo[3.2.1]octane ring system present in aurovertin-type natural products.

To date, quantitative analysis of proanthocyanidin (PAC) containing materials including plant extracts and fractions depends on colorimetric assays or phloroglucinolysis/thiolysis combined with UV-HPLC analysis. Such assays are of limited accuracy, particularly lack specificity, require extensive sample preparation and degradation, and need appropriate physical reference standards. To address this analytical challenge and toward our broader goal of developing new plant-sourced biomaterials that chemically and mechanically modulate the properties of dental tissue for clinical interventions, we have characterized 12 different PAC DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) materials. The DESIGNER approach is carried out by using either centrifugal partition chromatography (CPC) or size-exclusion chromatography (SEC) for the selective enrichment of trimeric and tetrameric PACs. Moreover, the rare but biologically interesting A-type PAC DESIGNERs can now be generated successfully from their natural AB-type PAC precursors via phenol-oxidative intramolecular coupling initiated by a mixture of the stable radicals, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Furthermore, to ensure the quality and stability of PAC DESIGNER materials, we developed a quantitative analysis of the total PAC content of the DESIGNER materials in the form of a quantitative NMR (qNMR) method using a non-PAC internal calibrant combined with diol-HPLC. The total PAC content was, thus, determined to be in a range of 67.5-96.9% by qNMR. We highlight the complementarity of diol-HPLC and qNMR to accurately assess the amount of PACs across a range of concentrations and PAC stability in the DESIGNER materials. This quantitative methodology paves the way to generate standardized DESIGNER and other PAC-containing materials and to perform rigorous quality control for dental (pre)clinical studies of PACs.

p-Terphenyl compounds are known to possess a diverse range of biological activities, making the synthesis of novel p-terphenyl derivatives a significant research objective. In this study, we report the first synthesis of nocarterphenyl A (1), characterized by a thiazole-fused p-terphenyl framework. Furthermore, we synthesized 18 additional analogs, including the naturally occurring compound 5-methoxy-4,7-bis(4-methoxyphenyl)benzo[d]thiazol-6-ol (9), employing a similar synthetic approach. Notably, compounds 12, 13, 15-17, and 19 demonstrated potent inhibitory effects against protein tyrosine phosphatase 1B (PTP1B), exhibiting IC₅₀ values ranging from 2.2 to 7.9 μM, which are lower than that of oleanolic acid (13.2 μM). Additionally, compound 14 was found to inhibit α-glucosidase from human colorectal adenocarcinoma (Caco-2) cells with an IC₅₀ value of 10.4 μM, which is also lower than that of acarbose (11.2 μM).

Living organisms synthesize various nonproteinogenic amino acids (NPAAs) as the building blocks of natural products. These NPAAs are often biosynthesized by pyridoxal 5'-phosphate (PLP)-dependent enzymes, which catalyze β- or γ- substitutions. These enzymes contribute to the structural diversification of NPAAs by installing new functional groups to amino acid side chains. Recent developments in genome mining have led to the identification of various PLP-dependent enzymes catalyzing β- or γ- substitutions, which form NPAAs in secondary metabolism. This short review summarizes recently investigated PLP-enzymes catalyzing β- or γ-substitutions in the biosynthesis of NPAAs by covering the literature published from 2015 through 2024.

Cannabidiol (CBD) is a natural product associated with a wide range of biological and therapeutic activities. Despite the widespread cultural acceptance of CBD as a medicinal agent, much remains to be determined regarding its precise mechanism(s) of action in treating multiple conditions. CBD has been shown to promiscuously interact with several neurological targets with varying affinities. To expand the chemical space of phytocannabinoids and develop novel chemical compounds, we have designed and synthesized a series of CBD and Δ⁸-THC homodimers, and CBD/Δ⁸-THC heterodimers. The capacity of the dimers to interact with a panel of CNS targets was explored along with the capacity to activate CB1 receptors, as measured by a GIRK channel activation assay. In the panel screen, the dimers were shown to be generally more active toward 5-HT2B and sigma 2 receptors with a range of K_i values from 0.6 to 8.7 μM. These findings provide early evidence that this new class of dimers can serve as novel chemical entities to explore receptor function and the potential for these dimers to have bivalent, bitopic, or dual mechanisms of action.