Search Results (985)

Two new chromone derivatives, cnidimols I and J (1 and 2), together with ten known aromatic derivatives (3–12), were isolated from the Beibu Gulf algicolous fungus Aspergillus versicolor GXIMD 02518. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations of 1 and 2 were accomplished by ECD calculations and X-ray diffraction analysis. Compound 1 was obtained as a pair of enantiomers, which were separated by chiral-phase HPLC analysis. Notably, 3,7-dihydroxy-1,9-dimethyldibenzofuran (6) displayed significant inhibition in LPS-induced NF-κB luciferase activity in RAW 264.7 macrophages, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophage cells. Full article

Background: Equol exists in two enantiomers of S-equol and R-equol. The results of cell and animal experiments, as well as clinical trials, have supported its protective effects on menopausal symptoms, aging, and cardiovascular diseases, especially S-equol, which is a naturally occurring, non-racemic isomer produced by intestinal bacteria. However, the selective response of host microorganisms to soy isoflavones limits the exploitation of equol-producing bacterial resources. Additionally, factors such as low efficiency, byproduct generation, and environmental pollution hinder the further development and the application of traditional equol synthesis techniques. Methods: Therefore, in this review, we aimed to describe the forms and scope of equol, key influencing factors (e.g., hydrogen and dietary factors) of in vivo and in vitro equol synthesis, and potential molecular mechanisms of equol produced by microorganisms. Notably, the traditional synthesis technology has effectively improved the synthesis efficiency of equol (85–96%), but the substrates and microbial species (such as Escherichia coli) remain the key influencing factors. Results: This review suggests that breakthroughs based on synthetic biology and gene editing technology will support the efficient in vitro synthesis of equol. Conclusions: This review serves as a valuable reference for future research. Full article

The naphthazarins shikonin and alkannan are strongly chromogenic, dark red enantiomers, each of which has biological activity, that are found primarily in the plant family Boraginaceae. These compounds and their many chemical metabolites, derivatives, oligomers, and analogs (“shikonoids”) are an important group of phytochemicals, utilized since antiquity as components of dyes, traditional medicines, and food and cosmetics. They are now recognized for their potent anti-inflammatory and regulatory activity on a variety of molecular signaling pathways in humans. Since many Boraginaceae species are overly exploited or endangered, we developed a pilot-scale in vitro shikonoid production system using Plagiobothrys arizonicus (Gray) Greene ex A.Gray, the Arizona popcorn flower, native to the southwestern USA and the Sonoran floristic province in the Madrean region of Mexico. Aseptic root cultures were initiated from fresh leaf tissue and stimulated to continuously produce shikonoids in liquid shake cultures layered under paraffin oil from which the shikonoids were extracted and concentrated. The crude, red extracellular product from these rapidly expanding root masses was also fractionated by Centrifugal Counter-Current Chromatography (CCC) into its component shikonin derivatives. A number of these shikonoids profoundly up-regulated detoxification and antioxidant proteins (phase 2 enzymes) and inhibited inflammation in mammalian cell bioassay systems. This prototype shikonoid production methodology can be readily scaled to either batch or chemostat culture. Full article

Propranolol is a non-selective β-adrenergic receptor antagonist widely used in cardiovascular and neurological therapy. Its naphthalene-based structure contributes to its high lipophilicityand central nervous system penetration. Clinically, propranolol is indicated for hypertension, arrhythmias, anxiety, migraine, and other conditions. It undergoes extensive hepatic metabolism via cytochrome P450 enzymes, notably CYP2D6, with a significant first-pass effect limiting oral bioavailability. This review integrates pharmacological profiling with crystallographic analysis to explore propranolol’s molecular interactions and therapeutic versatility. High-resolution crystal structures of the human β₂-adrenergic receptor (hβ₂-AR), particularly PDB ID: 6PS5 obtained via serial femtosecond crystallography (SFX), reveal key binding determinants responsible for receptor affinity and antagonism. Comparative structural analysis with other β-blockers—alprenolol, timolol, and carvedilol—highlights how variations in aromatic and heterocyclic frameworks influence pharmacokinetics and receptor selectivity. Superimposition results (RMSD: 0.032 for propranolol–alprenolol, 0.078 for propranolol–carvedilol, and 1.078 for propranolol–timolol) quantitatively illustrate molecular similarity and divergence. The enantioselective behavior of propranolol is also discussed, with the S-enantiomer showing greater receptor affinity and pharmacological potency than the R-form. Beyond canonical β-adrenergic targets, propranolol interacts with non-canonical proteins such as the cellulase enzyme Cel7A and lactoferrin, suggesting off-target effects and novel therapeutic potential. These findings underscore the importance of propranolol’s amphiphilic character, stereochemistry, and electrostatic properties in shaping its pharmacological profile. Overall, the integration of crystallographic data with pharmacological insights supports the rational design of next-generation β-adrenergic ligands with enhanced selectivity, bioavailability, and clinical efficacy. Full article

This study presents an enantiomeric-ratio-driven strategy for constructing mechanically robust supramolecular gels using cyclohexane bisurea derivatives. By employing non-equimolar enantiomeric mixtures, we achieved an ultralow critical gelation concentration (CGC < 2 mg/mL) in toluene, representing a reduction of more than fivefold compared to homochiral single-enantiomer systems. Rheological measurements revealed substantially enhanced mechanical properties in the non-equimolar gels, with yield stress and storage modulus values up to 17 and 20 times higher, respectively, than those of single-enantiomer gels. Morphological analyses (SEM and POM) indicated that pure enantiomers form isolated crystalline fibers with limited connectivity, whereas racemic mixtures yield disordered amorphous aggregates. In contrast, non-equimolar mixtures self-assemble into hierarchical “sea urchin-like” architectures, wherein crystalline fibers radiate from central cores to form densely interconnected networks. This unique structural motif underpins both the ultralow CGC and superior mechanical performance. Complementary FT-IR, XRD, and DSC analyses demonstrated that chiral imbalance modulates hydrogen-bonding interactions and structural order, while molecular dynamics (MD) simulations provided insight into the divergent self-assembly pathways among homochiral, racemic, and non-equimolar systems. This work provides a stereochemically guided approach for designing high-performance supramolecular gels with tailored hierarchical structures and enhanced functionality. Full article

The review is focused on dictyopterenes A, B, C, and D found in marine algae, covering their (a) distribution; (b) methods of isolation and identification; (c) absolute configuration; and (d) biosynthesis considerations. Dictyopterenes A and B are usually present in high amounts in Dictyopteris spp. Dictyopterene A was found to be abundant in D. prolifera, D. undulata, D. latiscula, D. polypodioides, and D. membranacea. Dictyopterene B (hormosirene) was found as the major compound in D. plagiogramma, D. australis, Hormosira banksii, D. potatorum, D. willana, D. antarctica, Xiphophora chondrophylla, X. gladiata, Scytosiphon lomentaria, Colpomenia peregrina, and Haplospora globosa. Dictyopterene C (dictyotene) was a major compound in D. undulata, D. prolifera, D. membranacea, Gomphonema parvulum, Amphora veneta, Phaeodactylum tricornutum, and D. vermicularis. Dictyopterene D (ectocarpene) was present in Ectocarpus siliculosus, Analipus japonicus, D. prolifera, D. undulata, and Sargassum linifolium. The following enantiomers were found: (1S,2R)-dictyopterene A, (1R,2R)-dictyopterene B, (1S,2S)-dictyopterene B, (1S,2R)-dictyopterene B, (R)-dictyopterene C, and (S)-dictyopterene D. In marine algae, C₁₁-hydrocarbons are derived from C₂₀ polyunsaturated fatty acids by the oxidative cleavage via, e.g., 9-hydroperoxyicosa-(5Z,7E,11Z,14Z,17Z)-pentaenoic acid. An alternative biosynthetic pathway for dictyopterene A and B via the proposed intermediates (S)-dictyoprolenols was considered by oxidative cleavage of hydroperoxyicosatetraenoic acid. Full article

Hydrogen bonding, a prevalent molecular interaction in nature, is crucial in biological and chemical processes. The emergence of single-molecule techniques has enhanced our microscopic understanding of hydrogen bonding. However, it is still challenging to track the dynamic behaviour of hydrogen bonding in solution, particularly under physiological conditions where interactions are significantly weakened. Here, we present a nanoscale-confined, functionalised quantum mechanical tunnelling (QMT) probe that enables continuous monitoring of electrical fingerprints of single-molecule hydrogen bonding interactions for over tens of minutes in diverse solvents, including polar physiological solutions, which reveal reproducible multi-level conductance distributions. Moreover, the functionalised QMT probes have successfully discriminated between L(+)- and D(−)-tartaric acid enantiomers by resolving the conductance difference. This work uncovers dynamic single-molecule hydrogen bonding processes within confined nanoscale spaces under physiological conditions, establishing a new paradigm for probing molecular hydrogen-bonding networks in supramolecular chemistry and biology. Full article

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment. Full article

The potential hazards of triazole fungicides to non-target organisms necessitate environmental risk assessment. This study, therefore, focused on characterizing the differential toxicity of the enantiomers of Ipfentrifluconazole (IFZ), a new triazole fungicide, in zebrafish larvae using a multi-endpoint approach. Acute toxicity tests determined the LC₅₀ values of 1.709 mg/L for rac-IFZ, 1.531 mg/L for (+)-IFZ, and 1.809 mg/L for (−)-IFZ, indicating a higher toxicity of the (+)-enantiomer. To avoid overt mortality while revealing organ-level effects, we chose a concentration of approximately 20% of the LC50 of (+)-IFZ, which is 340 μg/L, as the exposure concentration. Exposure to IFZ induced developmental defects, including swim bladder malformation, cardiac blood pooling, and metabolic disturbances during the early developmental stage of zebrafish. Additionally, cardiac and hepatic development and function were disrupted in zebrafish larvae following IFZ exposure. Biochemical and transcriptomic analyses revealed distinct toxic mechanisms: (+)-IFZ primarily disrupted lipid metabolism through alterations in PPAR signaling pathway and fatty acid degradation, while (−)-IFZ significantly impaired cardiac function by affecting adrenergic signaling in cardiomyocytes and cardiac muscle contraction. Rac-IFZ mainly influenced drug metabolism, particularly cytochrome P450-related pathways. These findings demonstrated the toxic effects of IFZ, emphasizing the need for evaluating environmental and health risks of chiral pesticides. The study provides valuable insights into the molecular mechanisms underlying IFZ toxicity. Full article

Aimed at addressing the increasingly serious problem of adulteration in Xihu Longjing, a catechin-targeted nano-enhanced visual and fluorescent dual-mode sensor array was constructed by nano porphyrins and quantum dots (QDs) for the precise analysis of Xihu Longjing from adjacent origins. This sensor array realizes the quantitative analysis of catechin enantiomers in Xihu Longjing through the selective combination of sensing units. It can accurately identify adjacent Xihu Longjing teas with different grades and storage times and can precisely detect samples with a low proportion of adulteration. At the same time, the flavor quality and antioxidant performance of Xihu Longjing tea can also be quantitatively evaluated. The dual-mode sensor array design proposed in this study provides a new idea for detecting minor differences in food authenticity and has significant application value for quality control in the tea industry. Full article

Alkanna tinctoria (L.) Tausch is a valuable medicinal plant known for its root-derived hydroxynaphthoquinone enantiomers, alkannin/shikonin (A/S), which exhibit significant pharmaceutical and cosmeceutical potential. However, its limited natural distribution and overharvesting pose conservation challenges, necessitating sustainable cultivation and extraction strategies. The application of Natural Deep Eutectic Solvents (NaDESs) has garnered significant attention as sustainable alternatives to conventional solvents. However, their toxicity in living plant systems remains largely unexplored. This study presents the successful establishment of an ex situ hydroponic cultivation system using the nutrient film technique (NFT) to grow A. tinctoria under greenhouse conditions. The system promoted plant acclimatization, vigorous root development, and initial production of A/S derivatives. In parallel, the toxicity evaluation of a bio-based NaDES, LeG_5_20 (levulinic acid–glucose, 5:1, with 20% water), applied as a circulating medium, was assessed. Physiological stress responses of the plants to NaDES circulation were assessed through non-destructive measurements, including stomatal resistance, photosynthetic and transpiration rates, and sub-stomatal CO₂ concentration. Short-term (24 min) exposure to NaDES showed no significant adverse effects, while longer exposures (4–8 h) induced marked stress symptoms and loss of leaf area. These findings demonstrate the feasibility of integrating green hydroponic systems with eco-friendly extraction solvents and provide a framework for further optimization of plant age, solvent exposure time, and system design to enable sustainable metabolite recovery without plant destruction. Full article

Tetrahydroprotoberberine alkaloids (THPBs) are bioactive natural products bearing stereogenic centers that frequently exhibit enantiomer-specific pharmacological effects. Xylopinine (XPN), a representative THPB, shows cytotoxic, antimicrobial, and antimalarial activity in vitro, and displays pronounced stereoselectivity in vivo, with the naturally occurring (S)-enantiomer emphasizing the need for reliable enantioselective analysis. In this study, we present the synthesis of racemic XPN from norlaudanosine, and its first comprehensive cyclodextrin-assisted capillary electrophoresis screening dedicated to the enantioseparation of XPN. Sulfated- and sulfobutyl-ether-β-cyclodextrin (S-β-CyD, SBE-β-CyD) provided efficient resolution (R_s > 3), while heptakis-(6-deoxy-6-(2-carboxyethyl)thio)-β-CyD (subetadex, SBX) yielded outstanding separation (R_s > 9). The enantiomer migration order was consistently R,S, except when using SBE-β-CyD, which showed the inverse sequence. Chiral HPLC using a Chiralpak AD column in polar organic mode with methanol modified with 0.1% diethylamine as mobile phase enabled the semi-preparative isolation of XPN enantiomers, with the (S)-enantiomer exceeding 95% purity. The absolute configuration was confirmed by circular dichroism spectroscopy. ¹H NMR titration and 2D rotating-frame nuclear Overhauser effect correlation spectroscopy (ROESY) consistently revealed multi-site recognition of XPN by SBX, supporting the inclusion of both aromatic rings (A and D). Full article

Background/Objectives: Fixed-dose combination (FDC) antihypertensive medications containing olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide are widely used for the treatment of essential hypertension. Although effective, the use of racemic amlodipine, which contains both active S(−)-amlodipine and inactive R(+)-amlodipine, has been associated with dose-dependent adverse effects, such as peripheral edema. S-amlodipine, a pharmacologically active enantiomer, provides comparable antihypertensive efficacy at half the dose with a lower incidence of side effects. Methods: In this study, a modified FDC formulation was developed by replacing racemic amlodipine with S-amlodipine to enhance tolerability while maintaining therapeutic efficacy. Results: A bilayer tablet design was employed to minimize the formation of impurities and ensure formulation stability, which was confirmed under stress and accelerated conditions. In vitro dissolution testing demonstrated pharmaceutical equivalence with the marketed reference FDC, and an in vivo pharmacokinetic study confirmed bioequivalence. Conclusions: These results suggest that the newly developed S-amlodipine besylate-containing FDC tablet is a viable alternative to existing olmesartan/amlodipine/hydrochlorothiazide combinations, offering comparable efficacy and pharmacokinetic properties with the potential for improved safety and patient adherence in the management of hypertension. Full article

Lipases are widely used as biocatalysts in synthetic applications because of their high chemo-, regio-, and enantioselectivities, which play key roles in the synthesis of esters and the resolution of racemates. These biocatalytic steps are essential for the production of various products, including cosmetic ingredients, building blocks in the pharmaceutical and agrochemical industries. In this study, we produced lipases through solid-state fermentation of agricultural by-products and domestic wastes using the fungus Pycnoporus sanguineus. After fermentation, the dried solids containing lipases from P. sanguineus exhibited high catalytic activity. Lipase production was achieved via solid-state fermentation using a substrate composed of wheat bran and sugarcane bagasse supplemented with either residual frying oil or urea, resulting in an enzymatic activity of 24 U mL⁻¹ after 96 h. The resulting P. sanguineus fermentation solids (PSFS) efficiently catalyzed the esterification of capric acid with ethanol, achieving 95% ester conversion within 28 h. Additionally, PSFS proved to be effective in the kinetic resolution of (RS)-1-phenyl-1-ethanol via transesterification with various acyl donors, selectively forming the (R)-enantiomer. This process yielded a 16% conversion to (R)-1-phenylethyl propionate and an enantiomeric ratio (E) exceeding 200 after 72 h. These results demonstrate the potential of PSFS for applications in ester synthesis and resolution of enantiomerically pure sec-alcohols. Full article

(±)-tiaprofenic acid (TA), marketed as (Surgam^®), belongs to the family of NSAIDs, with the peculiarity of a reduced incidence of ulcer induction in rats compared with parent drugs. However, some adverse effects were observed, and better knowledge of its interaction with biologic substrates is needed. Unfortunately, unlike most commercial NSAIDs, suitable single crystals for an X-ray diffraction study could not be obtained. To fill the gap, the crystal structure of TA was solved by X-ray powder diffraction, and the molecular interactions stabilizing the structure were analyzed by Hirshfeld surface and energy framework analysis. TA crystallizes in the $P{2}_1/c$ space group, with its two enantiomers in the asymmetric unit, further confirming the peculiarity of the crystal structure and the difficulty of solving it. TA packing is characterized by alternating enantiomers connected through hydrogen bonds, forming chains, arranged in layers, stabilized by $\pi$-stacking. First principle modeling revealed several stable conformations within 4$\mathrm{k}$$\mathrm{J}$ ${\mathrm{mol}}^{-1}$ of the global minimum and the relaxed potential energy scans revealed modest (8$\mathrm{k}$$\mathrm{J}$ ${\mathrm{mol}}^{-1}$ to 15$\mathrm{k}$$\mathrm{J}$ ${\mathrm{mol}}^{-1}$) energy barriers. Such flat energy landscape suggests flexible and dynamic behavior of tiaprofenic acid in solution and in vivo conditions, with multiple suitable docking sites. Full article