Search Results (54)

Microorganisms provide critical lead compounds for drug development, yet most biosynthetic gene clusters remain silent under standard culture conditions. The OSMAC strategy activates these clusters by adjusting cultivation parameters, thereby enabling the discovery of novel compounds from a single strain. Here, we applied OSMAC to explore the metabolic potential of the soft coral-derived fungus Aspergillus sclerotiorum SCSIO 41031. Three different culture media were employed for the large-scale fermentation process. After isolation by chromatography, the compounds were structurally characterized using NMR, MS, and X-ray single-crystal diffraction, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. In total, three new compounds, named 6,6′-diacetyl-1,1′-dihydroxy-3,3′-dimethoxydibenzyl ether (1), esterwortmannolol (17) and pestalpolyol I (20), along with 19 known compounds (2–16, 18–19 and 21–22) were obtained. This study validates the efficacy of the OSMAC strategy and underscores that A. sclerotiorum SCSIO 41031 serves as a valuable resource for producing structurally diverse natural products with potent biological activities. Full article

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. Results: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. Conclusions: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong–Vinegar cyperus rotundus drug pair. Full article

Aconitum pendulum Busch (Tiebangchui), a traditional Chinese medicinal herb, is recognized for its diverse pharmacological properties and for its significant toxicity. The Zanba stir-frying processing method is commonly employed to mitigate toxicity and enhance efficacy; however, the underlying chemical principles remain insufficiently studied. In order to address this issue, a phytochemical investigation was conducted on the diterpenoid alkaloids present in Zanba-processed Tiebangchui. Eleven diterpenoid alkaloids were isolated by means of chromatographic techniques, including silica gel column chromatography. Their structures were elucidated by extensive spectroscopic analysis (single-crystal X-ray diffraction, IR, HR-ESI-MS) and comparison with literature data. The compounds were identified as 12-epi-turpelline (1), 12-epi-napelline (2), 12-acetyl-napelline (3), azitine (4), flavaconitine (5), nagarutine C (6), nagarutine D (7), 16-epi-pyroaconine (8), spicatine B (9), 3-deoxyaconitine (10), and napelline (11). Notably, compound 1 was characterized as a novel alkaloid. Additionally, compounds 3–9 were isolated from this processed material for the first time. These findings provide crucial chemical insights into the detoxification mechanism of Zanba processing. Subsequent pharmacological evaluation revealed that compounds 10 and 11 exhibit notable anti-inflammatory activities. Moreover, given the structural analogy between the novel alkaloid 1 and the active compound 11, compound 1 is proposed as a promising lead for future structure–activity relationship studies and semi-synthetic modification. Full article

Levoglucosenone (LGO) smoothly undergoes microwave-assisted hetero-Diels–Alder reactions with thiochalcones in THF solution at 60 °C. The studied reactions are completed after 10 min, and the expected tricyclic 2,3-dihydro-4H-thiopyran derivatives are formed in a highly regio- and moderately stereoselective manner via competitive exo- and endo-attacks of the 1-thiadiene moiety onto the activated C=C bond of dienophile LGO. Although eight isomers are possible, only the formation of exo,exo- (major) and exo,endo- (minor) cycloadducts was observed. In most cases, isomeric products were separated by preparative layer chromatography and identified by means of spectroscopic methods. Some of the cycloadducts were obtained as single crystalline solids, and X-ray analyses enabled unambiguous confirmation of their structures. In order to explain the observed selectivity of the studied hetero-Diels–Alder reactions, DFT studies were carried out to determine the thermodynamic and kinetic properties of all regio- and stereoisomers. The results of these calculations predict the preferred formation of the two experimentally observed isomers. In addition, remarkable details on the electronic structure of E-1,3-diphenylprop-2-en-1-thione and on involved and hypothetical transition states could be elucidated. Full article

In recent years, we have observed a growing interest in molecular hybridization, which involves combining chemically and pharmacologically diverse fragments into a single molecule. In this study, we designed and synthesized a series of indole–pyrazole hybrids, variously substituted at the pyrazole ring. The compounds were characterized by spectroscopic methods, and the structures of most of them were confirmed by X-ray analysis. Reactions of 3-(dimethylaminomethyl)indole with bromo-methyl-pyrazole derivatives proceeded in a tautomer-selective mode: the 4-bromo-3(5)-methyl-((1H-pyrazol-1-yl)methyl)-1H-indole tautomers, obtained from the 4-bromo-3-methyl-1H-pyrazole, could be isolated by column chromatography. In contrast, the 3-bromo-5-methyl-1H-pyrazole yielded the ((5-bromo-3-methyl-1H-pyrazol-1-yl)methyl)-1H-indole as the dominant reaction product. The 3-bromo-5-methyl tautomer could not be isolated nor could its presence be identified in solution. However, traces of it were recognized in the crystal of 5-bromo-3-methyl tautomer as a binary solid solution. In silico studies provided the physicochemical parameters of all compounds, enabling the estimation of some derivatives affinity to certain enzymes. In vitro evaluation of the hemolytic and cytoprotective properties of all derivatives showed that most of the compounds exhibited no hemolytic activity, while all demonstrated significant cytoprotective effects on human erythrocytes under oxidative stress. Full article

Background/Objectives: Acute lung injury (ALI) is a respiratory disorder lacking specific targeted therapy. Our preliminary screening revealed that the ethanol extract of the seeds of Podocarpus nakaii (EESPN) alleviated the symptoms of ALI in mice. The objectives of this study were to identify the active constituents in EESPN and study the mechanism involved. Methods: Column chromatography was performed to separate the chemical constituents of EESPN. The structures of the isolates were determined via spectroscopic methods. MTT assays, Western blotting, histological analysis, TUNEL assays, immunofluorescence staining, transcriptomic analysis, and quantitative real-time polymerase chain reaction (qRT–PCR) were employed to evaluate the anti-inflammatory activity and to elucidate the potential mechanism of nagilactone C (3, Nag C) in ALI treatment. Results: Twelve compounds were isolated from EESPN and structurally characterized. The structure of podolactone E (1) was confirmed via single-crystal X-ray diffraction. In vitro, Nag C showed potent anti-inflammatory activity in LPS-induced RAW 264.7 cells. Nag C liposomes significantly ameliorated LPS-induced histopathological damage to the lungs, reduced neutrophil infiltration and inflammatory cytokine levels, increased myeloperoxidase (MPO) activity, and promoted apoptosis in mice. In addition to suppressing inflammation, Nag C also significantly suppressed the phosphorylation of the NF-κB, STAT3, and STAT1 proteins. Conclusions: Nag C is an active constituent of EESPN. It may protect against LPS-induced ALI via inhibition of the STAT signaling pathway. Thus, Nag C is a promising lead compound in the development of novel STAT-targeted anti-inflammatory agents. Full article

In this article, an efficient and straightforward protocol for the construction of complex dispirocyclic skeletons via regioselective intramolecular Michael addition is presented. Diverse dispirocyclic compounds were synthesized under mild and transition-metal-free conditions with good to excellent yields. Most stereoisomers were conveniently separated by column chromatography, and their relative configurations were identified by single-crystal X-Ray diffraction of representative compounds. A scale-up experiment validated the practicality of this method. In an in vitro assay, some dispirocyclic compounds exhibited potent cytotoxicity with an IC₅₀ value of 10⁻⁶ mol/L. Full article

Unguentaria are ancient vessels for oils, perfumes, ointments, or balms. Glass unguentaria are typically small in size and have long narrow necks to limit the loss of precious contents through spills and evaporation. The vessels may have single or double barrels. This study includes both double and single unguentaria from unprovenanced archaeological contexts. Residues found inside the vessels may reveal the original contents. Gas chromatography-mass spectrometry (GC-MS) and direct analysis in real time-mass spectrometry (DART-MS) were used to identify organic components of the residues, while headspace solid-phase microextraction (HS-SPME) gas chromatography mass spectrometry provided a method to target specifically the volatile aroma compounds. Inorganic compounds in the unguentaria residues were identified by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS). The results are consistent with a plant oil base, but few volatile perfume components could be characterized. While the collection of unguentaria may have contained perfumes, these results do not rule out the possibility of other unguents such as cosmetics. Full article

Marine Streptomyces are an important source of naturally occurring active compounds. Out of 23 marine Streptomyces strains, 1 strain of Streptomyces sp. FJ0218 was selected for its high activity in inhibiting α-glucosidase. Two polyketides, phaeochromycins D (2) and E (1), were isolated from the fermentation broth of this strain using bioactivity-guided column chromatography over RP-18, Sephadex LH-20, and silica gel. Their structures were determined using NMR data, HR-EI-MS, and single-crystal X-ray crystallography. Phaeochromycins D (2) and E (1) exhibited inhibitory activity against α-glucosidase, with IC₅₀ values of 10 mM and 25 mM, respectively. Lineweaver–Burk plots revealed that phaeochromycin E (1) acts as an uncompetitive inhibitor, while phaeochromycin D (2) acts as a non-competitive inhibitor. These findings suggest that there is potential for the pharmacological regulation of glucose levels through the use of polyketide phaeochromycins, emphasizing their significant impact on glucose management. Full article

The objective of this study was to evaluate the catalytic performance of commercial Nb₂O₅, supplied by CBMM, in the production of biodiesel by transesterification and esterification, using different feedstocks (soybean, corn, sunflower, and waste oils) and both methyl and ethyl routes. For this, the catalyst was characterized in terms of its crystal structure by X-ray diffraction (XRD), specific surface area using the Brunauer–Emmett–Teller (BET) technique, thermal stability by thermogravimetric analysis (TGA), morphology by scanning electron microscopy (SEM), acidity by ammonia desorption at programmed temperature (TPD-NH₃), and catalytic activity by gas chromatography. The results from the structural analyses indicated that Nb₂O₅ has a single monoclinic phase and a morphology consisting of irregular agglomerates. The specific surface area was 1.3 m²/g, and its density was 4.639 g/cm³. The thermogravimetric analysis showed that the material has thermal stability, maintaining its structural integrity up to temperatures as high as 1000 °C. The total acidity reached 301 μmol NH₃/g, indicating the presence of Brønsted and Lewis acidic sites. In catalytic tests, Nb₂O₅ showed higher efficiency in the methyl route, achieving an initial conversion of 96.43% in esters with soybean oil, outperforming other feedstocks. However, catalyst reuse over five cycles revealed a progressive decrease in catalytic activity, possibly due to blocking active sites by adsorbed products, as confirmed by FTIR and XRD analyses conducted on the catalyst. Despite decreased activity after the cycles, the catalyst maintained its crystal structure, indicating structural stability. These results demonstrate the potential of Nb₂O₅ as a heterogeneous catalyst for biodiesel production, particularly with the methyl route and high-quality oils. This study highlights the relevance of Nb₂O₅ in biodiesel synthesis, contributing to sustainable practices and technological advancement in the renewable energy sector. Full article

Single enzymatic modifications are limited to starch. Complex modification with synergistic amylases will improve starch properties more significantly. In this study, maize starch was compound modified by β-amylase and α-glucosidase. The structure and physicochemical properties of the corn starch were determined by scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT–IR), proton nuclear magnetic resonance hydrogen spectroscopy (¹HNMR), high-performance anion-exchange chromatography (HPAEC–PAD), differential scanning calorimetry (DSC) and Rapid Visco analyzer (RVA) to determine the changes in the structure and physicochemical properties of maize starch before and after the dual enzyme modification. The branching degree (4.95–7.10%) of maize starch was increased after bi-enzymatic modification, the amylose content (28.77–18.60%) was decreased, and the amylopectin content (70.79–81.71%) was elevated. The relative crystallinity (20.41–30.20%) and short-range ordered structure of the starch increased, and the dual enzyme modification led to a more compact structure. Dual enzyme-modified maize starch showed a decrease in long chains, an increase in short chains, and its degree of branching was elevated. Dual enzyme modification also affected the thermal stability, pasting, light transmittance (1.40–2.16%), solubility (20.15–13.76%), and swelling (33.97–45.79%) of maize starch. It can be concluded that the complex modification of maize starch by β-amylase and α-glucosidase significantly changed the amylose/amylopectin ratio of the starch and made its structure denser. These results can provide a theoretical basis for the enzymatic preparation of maize starch with different amylose/amylopectin ratios and the development and utilization of functional starches. Full article

(R)-2-Amino-1-hydroxyethylphosphonic acid 2 was prepared by hydrolytic kinetic resolution of rac-diethyl oxiran-2-ylphosphonate followed by reaction with benzylamine, acid hydrolysis, catalytic hydrogenolysis, and anion-exchange chromatography. Recrystallization from water-ethanol gave pure 2, which was characterized by IR, ¹H NMR, ¹³C NMR, ³¹P NMR, polarimetry, elemental microanalysis, high-resolution mass spectrometry, and single-crystal X-ray diffraction. The acid 2 crystallized in the orthorhombic noncentrosymmetric space group P2₁2₁2₁ with cell parameters a = 6.303 (2) Å, b = 7.104 (2) Å, c = 11.627 (3) Å. The X-ray crystal structure confirmed the (R)-configuration of 2 and revealed that 2 is zwitterionic in the solid state, with extensive intermolecular hydrogen bonding between the hydroxyl, ammonium cation, and phosphonate anion groups. Full article

Norfloxacin (NORF) is a broad-spectrum quinolone that is widely utilized for the treatment of various bacterial infections and is considered one of the most commonly used fluoroquinolone antibiotics. However, NORF’s clinical utility is limited by its poor water solubility and relatively low oral bioavailability. This study presents an optimization and synergistic enhancement approach through salt/co-crystal, aiming to maximize the biopharmaceutical properties of NORF with the use of phenolic acid. Following this strategy, two new hydrate salts of NORF with phenolic acid, namely, NORF—3,5-DBA hydrate (salt 1) and NORF—VA hydrate (salt 2), were prepared and systematically confirmed. Two hydrate salts were produced by means of the slow evaporation crystallization method, and the structures were determined through single-crystal X-ray diffraction (SCXRD). Additionally, powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and high-performance liquid chromatography (HPLC) were applied to analyze the features of the two salts. The experimental results indicated that the formation of the two salts could enhance the solubility and improve the release behavior of NORF. Interestingly, the physicochemical properties of NORF were significantly improved as a result, leading to an enhancement in its antibacterial activity. This was demonstrated by the enhanced inhibition of bacterial strains and the lower minimum inhibitory concentration values. Full article

Herein, we describe the first consistent regiospecific reaction of isothiocyanates with a variety of substituted N-arylcyanothioformamides in a 1:1 molar ratio to generate a series of imidazolidineiminodithiones decorated with a multitude of functional groups on both aromatic rings. The reaction is carried out at room temperature using a 20 mol% catalytic amount of triethylamine with DMF as the solvent to selectively form the mentioned products with exclusive regioselectivity. The methodology features wide substrate scope, no requirement for chromatography, and good to high reaction yields. The products were isolated by simple ether/brine extraction and the structures were verified by multinuclear NMR spectroscopy and high accuracy mass measurements. The first conclusive molecular structure elucidation of the observed regioisomer was established by single-crystal X-ray diffraction analysis. Likewise, the tautomer of the N-arylcyanothioformamide reactant was proven by X-ray diffraction analysis. Density functional theory computations at the B3LYP-D4/def2-TZVP level in implicit DMF solvent were conducted to support the noted regiochemical outcome and proposed mechanism. Full article

Diisoamyl (1R,4S)-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate (2) was prepared by reacting exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (1) with isoamyl alcohol in the presence of a sulfuric acid catalyst under sonication conditions. Compound 2 was characterized by ¹H, ¹³C NMR, DEPT-135, infrared, and UV-vis spectroscopy. Gas chromatography–mass spectrometry, elemental analysis, and melting point determination were used to assess purity. The structure of compound 2 was also determined by single-crystal X-ray diffraction. It crystallizes in the monoclinic space group P2₁/c (14) with cell values of a = 15.5647(3) Å, b = 12.8969(2) Å, c = 9.0873(2) Å; β= 99.3920(10)°. Full article