Chemistry & Biodiversity最新文献

Flavonoids represent a distinct category of therapeutic compounds characterized by a wide range of pharmacological properties. Rutin, a naturally occurring flavonoid, is prevalent as an active constituent in various vegetables, fruits, and herbs commonly consumed in daily diets. Rutin demonstrates a broad spectrum of pharmacological effects, including antioxidant activity, anti-inflammatory properties, antidiabetic potential, and anticancer capabilities. In addition, it offers protective benefits to the nervous system and vital organs, positioning it as a promising candidate for the treatment of numerous diseases and underscoring its significant therapeutic potential. Despite the low toxicity, safety, and cost-effectiveness of rutin analogs, their clinical application is restricted by poor water solubility and limited permeability, resulting in low oral bioavailability. Moreover, there is a paucity of studies addressing the toxicity, pharmacokinetics, and clinical applications of rutin. Therefore, this paper provides a comprehensive review of rutin's pharmacological actions, pharmacokinetic properties, toxicity profile, and clinical applications, with the objective of enhancing our understanding of this compound. It seeks to lay the foundation for the development and application of natural therapeutic agents.

Three previously undescribed diterpenoids and a new sesquiterpenoid, along with 31 known terpenoids, were isolated from the leaves and twigs of Cryptomeria japonica. Their structures were elucidated by spectroscopic data and ECD calculations. Antibacterial screening of all isolated compounds was conducted. Compounds 15 and 16 exhibited modest activity against drug-resistant Staphylococcus aureus subsp. aureus ATCC29213, with MIC₅₀ values of 3.57 ± 0.03 and 8.69 ± 0.03 µM, respectively.

The study investigated Dactylonectria torresensis as a sustainable source of podophyllotoxin (PTOX), a key precursor for anticancer drugs such as etoposide and teniposide. The fungus was identified through morphological analysis and ITS rDNA sequencing. PTOX from the fungal extract was isolated and characterized using high-performance liquid chromatography, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. Antioxidant activity was evaluated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assays, showing comparable 50% inhibition (IC₅₀) values for standard and fungal PTOX – 297.4 versus 309.8 µg/mL (DPPH) and 306.6 versus 316.3 µg/mL (reducing power). Cytotoxicity against MCF-7 breast cancer cells also revealed similar IC₅₀ values: 3.083 µM for standard and 3.188 µM for fungal PTOX. PTOX production was optimized through a two-phase statistical approach: Plackett-Burman Design followed by Face-Centered Central Composite Design. Initially, D. torresensis produced 78.46 µg/g dry weight (DW) of PTOX, which increased 6.35-fold to 498.76 µg/g DW after optimization.

Justicia betonica L. (Acanthaceae) is a traditionally used medicinal plant with limited evidence on its anticancer mechanisms. This study integrates phytochemical profiling, molecular docking, and in vitro/in vivo evaluations to elucidate its anticancer potential. Gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) analyses identified a diverse phytochemical repertoire, including retronecine, maritimetin, hematopodin, mangiferin 6′-gallate, and quercetin glycosides, many reported here for the first time in J. betonica L. In silico docking revealed high binding affinities of these constituents toward multiple oncogenic targets—CDK-2, CDK-6, B-cell lymphoma 2 (Bcl-2), vascular endothelial growth factor receptor-2 (VEGFR-2), and insulin-like growth Factor 1 receptor (IGF-1R)—suggesting multi-target inhibitory potential. The ethanolic extract of J. betonica L. exhibited selective cytotoxicity against MCF-7, A549, and HT29 cell lines, with IC₅₀ values of 42.11 ± 1.64, 35.39 ± 1.02, and 29.66 ± 1.34 µg/mL, respectively, while sparing normal human umbilical vein endothelial cells (HUVECs). Acute toxicity studies confirmed safety up to 2000 mg/kg. In the Ehrlich ascites carcinoma (EAC) model, oral administration of EEJB (400 mg/kg) significantly reduced tumor volume, packed cell volume, and viable cell count, extended mean survival time, and ameliorated tumor-induced hematological and hepatic alterations. These findings position J. betonica L. as a promising plant-derived, multi-target anticancer candidate, meriting further isolation of active principles and mechanistic exploration.

A new snyderane-type sesquiterpene, argusene (1), and 10 known terpenes, 3,3-dimethyl-5-methylene-4-(3-methylpenta-2,4-dien-1-yl)cyclohex-1-ene (2), luzonensol (3), palisadin B (4), 12-hydroxypalisadin B (5), 12-acetoxypalisadin B (6), palisadin A (7), aplysistatin (8), pacifigorgiol (9), debromolaurinterol (10), and 3-bromobarekoxide (11), were isolated from the sea hare Aplysia argus collected from Ikei Island in Okinawa Prefecture, Japan. Their structures were established using spectroscopic methods such as infrared, nuclear magnetic resonance, and high-resolution-electrospray ionization-mass spectrometry. Since all these compounds were derived from a particular red alga, it was determined that this sea hare targets this red alga for feeding, thereby confirming a specific dietary relationship. The cytotoxicity of 1–11 against the human hepatoma cell line HepG2 was evaluated, and 1, 4, 5, 6, 7, 8, 10, and 11 decreased cell viability in a concentration-dependent manner. In addition, intracellular lipid accumulation induced by free fatty acid treatment in serum-free medium was significantly suppressed in the presence of 8 (5.0 µg/mL).

Twelve monoterpene indole alkaloids (1‒12), classified into six diverse types, ajmalicine (1, 3, and 4), tubotaiwine (2), aspidosperma (5 and 6), peraksine (7 and 8), eburnane (9 and 10), and heteroyohimbine (11 and 12), respectively, were isolated from the branches and leaves of Alstonia mairei. Their structures were elucidated via the spectroscopic data interpretation, electronic circular dichroism calculations, single crystal X-ray diffraction analysis, and comparison with literature. Notably, mareines C (1) and D (2) represent the first examples of the natural ajmalicine alkaloid possessing an additional carbon connecting with C-3 and 12-hydroxytubotaiwine alkaloid, respectively. Compounds 3 and 6‒12 were obtained from Alstonia mairei for the first time. In addition, all isolates were evaluated for their anti-inflammatory activities in vitro, and compounds 1, 4, 7/8, 11, and 12 exhibited potent inhibitory activities on the lipopolysaccharide-induced nitric oxide production in RAW264.7 mouse macrophages with IC₅₀ values ranging from 4.4 to 20.4 µM.

Fungal-derived natural compounds serve as a crucial resource for new drug development and have witnessed significant progress in recent years. Researchers have screened multiple bioactive compounds from fungal extracts. Epilepsy, a neurological disorder affecting tens of millions of people worldwide, presents substantial therapeutic challenges due to its complex pathogenesis. Neuronal apoptosis plays a critical role in epileptogenesis and seizure generation. In this study, we screened a fungal-derived natural compound, chaetosemin J, with antiepileptic activity using zebrafish and cell models. Screening assays using the zebrafish model demonstrated that chaetosemin J alleviated epileptiform behavior and downregulated seizure-induced epilepsy marker genes. In parallel, cell-based assays showed that chaetosemin J enhanced cell viability. The anti-epileptic pathways and associated targets of chaetosemin J were predicted using transcriptomics and molecular docking techniques. Furthermore, its anti-epileptic mechanism was validated through real-time quantitative polymerase chain reaction experiments and calcium ion reflow assays. Collectively, our findings suggested that chaetosemin J may alleviate epileptic seizures by downregulating the expression of integrin-related genes in the extracellular matrix/focal adhesion signaling pathway, reversing the abnormal elevation of intracellular calcium ion concentration during epileptic seizures, and thereby reducing the activation of the apoptosis-related factor Calpain-2. This study provides a new candidate molecule for the development of antiepileptic drugs.

A series of novel hybrids of dehydroabietic acid (DHA) with semi-, thiosemicarbazides, and amino-1,3,4-oxadiazoles was synthesized starting from respective thioisocyanates or isocyanates. The cyclodehydrosulfurization of thiosemicarbazides with Hg(OAc)₂ was used as a fast and efficient method to obtain regioisomeric 2-alkyl(aralkyl, aryl)amino-5-terpenyl- and 2-terpenylamino-5-alkyl(aralkyl, aryl)-1,3,4-oxadiazoles, even in the case of sterically hindered dehydroabietyl derivatives. Several conformationally flexible acylthiosemicarbazide and 2-amino-1,3,4-oxadiazole hybrids exhibited cytotoxicity against HepG2, MCF-7, and HeLa tumor cell lines that was significantly superior to that of the parent DHA. Among them, 2-(abieta-8,11,13-trien-18-oyl)-N-phenylhydrazincarbothioamide was the most active (GI₅₀ = 12–17 µM), inhibiting the growth of tumor cells with greater selectivity (SI = 4.6–7.2) than doxorubicin, a positive control. The thiosemicarbazide moiety in the molecules of the acylthiosemicarbazide hybrids was important for the inhibition of the tumor cells’ growth, while its adjacement mode to the terpenyl fragment was tolerant for retaining cytotoxicity. Replacement of the sulfur-containing thiosemicarbazide moiety with the sulfur–free semicarbazide resulted in the loss of cytotoxic properties. Absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized hybrids were assessed in silico.

Black myrtle (Myrtus communis L.) is a valuable raw material for the functional food industry due to its rich phytochemical composition and strong antioxidant potential. However, a significant research gap exists regarding the integrated impact of industrial processing and gastrointestinal (GI) digestion dynamics on the bioaccessibility of these bioactive compounds. The aim of the study was to optimize the extraction conditions of pasteurized and concentrated clear myrtle juice, to monitor changes in total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacities (2,2-diphenyl-1-picrylhydrazyl [DPPH], 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) [ABTS], ferric reducing antioxidant power [FRAP], and cupric ion reducing antioxidant capacity [CUPRAC]) during processing, and to evaluate the bioaccessibility of these properties under in vitro GI digestion. Production protocols were mathematically validated utilizing response surface methodology (RSM), in vitro GI simulations, and principal component analysis (PCA)-based multivariate analysis. The findings confirmed that optimized extraction conditions maximize bioactive recovery. Pasteurization significantly (p < 0.05) enhanced phenolic bioaccessibility compared to concentrated juices by facilitating matrix destabilization. Conversely, thermal concentration induced substantial anthocyanin degradation, whereas the high antioxidant potential retained in the pomace underscored its viability for value-added valorization. These findings provide critical technological and industrial implications, indicating that mild thermal processing offers a strategic pathway for formulating black myrtle as a scientifically substantiated nutraceutical ingredient while supporting the development of innovative, functionally optimized beverage products.

This study investigated the bioactive composition and antifungal efficacy of neem seed extracts (NSE) prepared using acetone, ethyl acetate, chloroform, methanol, and ethanol against Aspergillus parasiticus and Aspergillus flavus. Gas chromatography–mass spectrometry (GC–MS) analysis revealed solvent-specific compounds profiles: ethanol extract contained 35 bioactive compounds (mainly esters and fatty acids), dominated by n-hexadecanoic acid (28.65%); methanol extract had 29 diketopiperazines, with 3,6-bis(2-methylpropyl)-2,5-piperazinedione (45.45%) as major; chloroform, ethyl acetate, and acetone extracts featured long-chain esters, hydrocarbons, and 2-heptadecanone (33.15%), respectively. All extracts inhibited fungal growth at 500 mg/mL, whereas ethanol was most effective at 31.25 mg/mL, reducing mycelial biomass by 45%. Methanol and ethanol extracts (250 mg/mL) suppressed aflatoxin (AF) (AFB₁, AFB₂) production by >90%. Six-month feed trials confirmed neem seed powder (NSP) as a potent biopreservative, achieving complete AF inhibition at 30% concentration. These findings highlight neem's potential as a natural antifungal and anti-aflatoxigenic agent.