Search Results (37)

The study of various microorganisms isolated from an Indian Ocean sponge, Scopalina hapalia ML-263, led to the selection of a promising Actinobacteria strain, Micromonospora sp. SH-82. Genomic analysis identified this strain as a new species, revealing the presence of 23 biosynthetic gene clusters (BGCs), some of which are associated with the synthesis of specialized metabolites such as polyketides deriving from polyketide synthases (PKSs). The strain was cultivated under favorable conditions for the production of bioactive molecules, resulting in the isolation and identification of seven microbial metabolites. Three of them are potentially novel, two erythronolides and one erythromycin, all characterized by a rare C10–C11 double bond. Some of these compounds also display atypical conformations, forming hemiacetals or spiroacetals. Their identification was achieved through detailed chemical analyses (NMR and ESI⁺-HRMS). A molecular networking approach was employed to assess the presence of potentially novel molecules in the microbial crude extract, supported by the identification of isolated molecules. Four molecules (1, 2, 3 and 5) were evaluated for their cytotoxic activities against cancer cell lines (HCT-116 and MDA-MB-231) and the immortalized retinal pigment epithelial RPE1 cells. No activity was observed in the latter, suggesting a lack of toxicity toward healthy cells. Moreover, megalomicin C1 (3), one of the isolated compounds, showed interesting antiplasmodial activity against Plasmodium falciparum 3D7, with an IC₅₀ of 6.37 ± 2.99 µM. Full article

The role of p-benzoquinone (BQ) as a photocatalyst in the synthesis of solketal under UV irradiation has been studied, along with the combined use of BQ/TiO₂ P25 as a photocatalytic system for the process. The presence of the O₂/O₂^−• redox couple is essential for the reaction to take place. However, experiments with p-benzoquinone as a superoxide radical scavenger failed, with the opposite effect of enhancing the reaction being observed. It was found that p-benzoquinone and oxygen compete for photogenerated electrons in the conduction band of titania. A redox equilibrium between p-benzoquinone and hydroquinone (H₂Q), mediated by the O₂/O₂^−• system, was identified as a key factor in enabling the reaction. Furthermore, EPR spin-trapping experiments confirmed the presence of the carbon-centered radical 2-hydroxypropan-2-yl, which was determined to be the main radical species involved in the process. Either acetone or 2-propanol can generate this radical, with the BQ/H₂Q redox system being pivotal in the formation of the hemiacetal intermediate. This intermediate is subsequently converted into the final acetal (solketal), with H₂Q acting as a photoacid through an excited-state proton transfer (ESPT) mechanism. The photoacid behavior of hydroquinone was confirmed using pyridine as a basic probe, as the formation of hydroquinone–pyridine adducts was detected by Raman spectroscopy. Full article

The rapidly growing glycoscience has boosted the research on the synthesis of glycans and their conjugates, which are centered on the stereoselective formation of glycosidic bonds. Compared to the mainstream acid-promoted glycosylation method that undergoes the S_N1 type mechanism, the basic/neutral conditions give better stereo control via the S_N2 mechanism. Anomeric hydroxyl group transformation, whether to form glycosidic bonds directly or to install a leaving group for later glycosylation, is key to carbohydrate synthesis, and the strategies in the stereo control of these reactions under basic/neutral conditions are summarized in this review. Different stereo control strategies that are applicable to protected or unprotected hemiacetals are discussed, and case-by-case studies of literature reports in the past two decades are included. In addition to surveying literature reports, this review aims at providing insights into the strategic considerations in the development of a stereoselective method for the formation of glycosidic bonds. Full article

The herb Curculigo capitulata (Lour.) Ktze is widely distributed in southern and southwestern China. The Curculigo genus and its primary chemical constituents exhibit remarkable antidepressant activities. To investigate the chemical constituents and potential health benefits of C. capitulata, a phytochemical study was conducted. In this study, seven new compounds (capitugenin A–G), including three new norlignans (1–3), a new chalcone dimer (4), a new hemiacetal (5), two novel pyrrolidine-based compounds (6 and 7), including one identified as a natural product (7), and nineteen known compounds (8–26), were isolated from C. capitulata. The chemical structures and absolute configurations of Compounds 1–7 were elucidated via comprehensive spectroscopic data analyses. The neuroprotective effects of Compounds 1–26 against glutamate-induced cell death were tested in the human neuroblastoma cell line SH-SY5Y. Compounds 1, 3, 6, 8, 11, and 17 showed significant neuroprotective effects, with protection rates ranging from 29.4 to 52.8% at concentrations ranging from 5 to 40 μM. Western blot analysis indicated that Compound 3 exerted a protective effect by regulating the expression of Nrf2/HO-1. Full article

Alginates play an important role in the resistance of mucoid strains of Pseudomonas aeruginosa to antibiotics, as well as their persistence by escaping the immune defense system. GDP-mannose dehydrogenase (GMD) is the key enzyme in alginate biosynthesis by catalyzing the irreversible double oxidation of GDP-mannose to GDP-mannuronate. GDP-mannose dehydrogenase purified from mucoid strains exhibits strong negative cooperativity for its substrate, the GDP-mannose, with a K_M of 13 µM for the site of strong affinity and 3 mM for this weak of a binding. The presence of a nucleotide strongly associated with the enzyme was detected, confirming the fact that the substrate oxidation reaction takes place in two distinct steps, with the substrate blocked on the enzyme in a half-oxidation state in the form of a hemiacetal. As the GMD polypeptide has only one site for substrate binding, our results tend to confirm the fact that the enzyme functions in a dimer form. The GDP-mannose dehydrogenase inhibition strategy that we developed a few years ago, based on the synthesis of substrate analogs, has shown its effectiveness. The addition of an alkynyl radical on carbon 6 of the mannose grafted to an amino-sulfonyl-guanosine allows, at a concentration of 0.5 mM, to inhibit GMD by 90%. As we had previously shown the effectiveness of these analogs on the sensitivity of mucoid strains of Pseudomonas aeruginosa to aminoglycosides, this revives the interest in the synthesis of new inhibitors of GDP-mannose dehydrogenase. Full article

A facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-a]pyridines at room temperature via the HFIP-promoted Friedel–Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-a]pyridines. This strategy could be applied to the direct C(sp²)-H hydroxydifluoromethylation of imidazo[1,2-a]pyridines and afford a series of novel difluoromethylated carbinols in good to satisfactory yields with 29 examples. Furthermore, gram-scale and synthetic transformation experiments have also been achieved, demonstrating its potential applicable value in organic synthesis. This green protocol has several advantages, including being transition metal- and oxidant-free, being carried out at room temperature, having high efficiency, and having a wide substrate scope. Full article

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10–12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2–5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC₅₀ values as low as 5.82 ± 0.18 μM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions. Full article

Laboratory rabbits are fed foods rich with cationic metals, and while fasting cannot empty gastric contents because of their coprophagic habits. This implies that, in rabbits, the oral bioavailability of chelating drugs could be modulated by the slow gastric emptying rates and the interaction (chelation, adsorption) with gastric metals. In the present study, we tried to develop a rabbit model with low amounts of cationic metals in the stomach for preclinical oral bioavailability studies of chelating drugs. The elimination of gastric metals was achieved by preventing food intake and coprophagy and administering a low concentration of EDTA 2Na solution one day before experiments. Control rabbits were fasted but coprophagy was not prevented. The efficacy of rabbits treated with EDTA 2Na was evaluated by comparing the gastric contents, gastric metal contents and gastric pH between EDTA-treated and control rabbits. The treatment with more than 10 mL of 1 mg/mL EDTA 2Na solution decreased the amounts of gastric contents, cationic metals and gastric pH, without causing mucosal damage. The absolute oral bioavailabilities (mean values) of levofloxacin (LFX), ciprofloxacin (CFX) and tetracycline hydrochloride (TC), chelating antibiotics, were significantly higher in EDTA-treated rabbits than those in control rabbits as follows: 119.0 vs. 87.2%, 9.37 vs. 13.7%, and 4.90 vs. 2.59%, respectively. The oral bioavailabilities of these drugs were significantly decreased when Al(OH)₃ was administered concomitantly in both control and EDTA-treated rabbits. In contrast, the absolute oral bioavailabilities of ethoxycarbonyl 1-ethyl hemiacetal ester (EHE) prodrugs of LFX and CFX (LFX-EHE, CFX-EHE), which are non-chelating prodrugs at least in in vitro condition, were comparable between control and EDTA-treated rabbits irrespective of the presence of Al(OH)₃, although some variation was observed among rabbits. The oral bioavailabilities of LFX and CFX from their EHE prodrugs were comparable with LFX and CFX alone, respectively, even in the presence of Al(OH)₃. In conclusion, LFX, CFX and TC exhibited higher oral bioavailabilities in EDTA-treated rabbits than in control rabbits, indicating that the oral bioavailabilities of these chelating drugs are reduced in untreated rabbits. In conclusion, EDTA-treated rabbits were found to exhibit low gastric contents including metals and low gastric pH, without causing mucosal damage. Ester prodrug of CFX was effective in preventing chelate formation with Al(OH)₃ in vitro and in vivo, as well as in the case of ester prodrugs of LFX. EDTA-treated rabbits are expected to provide great advantages in preclinical oral bioavailability studies of various drugs and dosage formulations. However, a marked interspecies difference was still observed in the oral bioavailability of CFX and TC between EDTA-treated rabbits and humans, possibly due to the contribution of adsorptive interaction in rabbits. Further study is necessary to seek out the usefulness of the EDTA-treated rabbit with less gastric contents and metals as an experimental animal. Full article

The influence of the solvent in the reaction of dysprosium(III) chloride hydrate with the N₃O₂ ligand H₂L (2,6-bis(2-hydroxyphenyliminomethyl)pyridine) was studied To this end, the new mononuclear chloride complex [Dy(L)Cl(H₂O)₂] (1) was isolated in absolute ethanol as solvent, without any evidence of the hydrolysis of the ligand. This clearly contrasts with previous results, where a similar reaction in methanol proceeds with the partial hydrolysis of the Schiff base, and the formation of a new hemiacetal donor to yield [Dy(HL’)₂)][Dy(L)(Cl₂)] (H₂L’ = (6-(2-hydroxyphenyliminomethyl)-2-methoxyhydroxymethyl)pyridine). The single crystal X-ray structure of the chloride complex 1 shows that the Dy^III ion is octacoordinated in a highly distorted N₃O₄Cl environment between triangular dodecahedral and biaugmented trigonal prisms. The full magnetic characterisation of 1 shows that it presents field-induced single ion magnet behaviour, with a thermal energy barrier U_eff of 113.5 K, which is the highest among dysprosium complexes derived from H₂L. Full article

Sclareolide is a sesquiterpene lactone isolated from various plant sources in tons every year and is commercially used as a flavor ingredient in the cosmetic and food industries. Antitumor and antiviral activities of sclareolide have been previously reported. However, biological studies of sclareolide synthetic analogous are few. In view of these, we developed a robust synthetic method that allows the assembly of 36 novel sclareolide-indole conjugates and their derivatives. The synthetic method was based on TiCl₄-promoted nucleophilic substitution of sclareolide-derived hemiacetal 4, while electron-rich aryles including indoles, polyphenol ethers, and pyrazolo [1,5-a]pyridine were good substrates. The stereochemistry of the final products was confirmed by single-crystal X-ray diffraction analysis, while the antiproliferative activities of selected final products were tested in K562 and MV4-11 cancer cell lines. Cytometric flow analysis shows that lead compounds 8k- and 10-induced robust apoptosis in MV4-11 cancer cells, while they exhibited weak impact on cell cycle progression. Taken together, our study suggests that sclareolide could be a good template and substrate for the synthesis of novel antiproliferative compounds. Full article

GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1’s transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in Xenopus laevis oocytes. All the mutants decreased the uptake of both substrates to less than 50%. The partial effect of the N317A mutant in transporting dehydroascorbic acid was associated with a 30% decrease in the V_max compared to the wildtype GLUT1. The results show that both substrates share the eight residues studied in GLUT1, albeit with a differential contribution of N317. Our work, combining docking with functional studies, marks the first to identify structural determinants of oxidized vitamin C’s transport via GLUT1. Full article

The impetus for research into hydrogels based on selectively oxidized polysaccharides has been stimulated by the diversity of potential biomedical applications. Towards the development of a hemostatic wound dressing in this study, we creatively combined the (hemi)acetal and Schiff base bonds to prepare a series of multifunctional cryogels based on dialdehyde pullulan and dopamine. The designed structures were verified by NMR and FTIR spectroscopy. Network parameters and dynamic sorption studies were correlated with environmental scanning microscopy results, thus confirming the successful integration of the two components and the opportunities for finely tuning the structure–properties balance. The viscoelastic parameters (storage and loss moduli, complex and apparent viscosities, zero shear viscosity, yield stress) and the structural recovery capacity after applying a large deformation were determined and discussed. The mechanical stability and hemostatic activity suggest that the optimal combination of selectively oxidized pullulan and dopamine can be a promising toolkit for wound management. Full article

SCOBY bacterial cellulose (BC) is a biological macromolecule (considered as a by-product) that grows at the liquid–air interface during kombucha tea fermentation. In this study, BC:HC (hydrolyzed collagen) blend films coated with 1 wt% chitosan (CS) were loaded with ascorbic acid to study loading/releasing performance. At first, the mechanical properties of the blend films were found to be dependent on HC ratio. After chitosan coating, the coated films were stronger due to intermolecular hydrogen bonding interaction and the miscibility of two matrixes at the interface. The antibacterial activity test according to the AATCC Test Method revealed that chitosan-coated BC/HC films exhibited excellent antimicrobial activity against S.aureus growth from the underneath and the above film when compared to BC and BC:HC films. Moreover, chitosan was attractive to ascorbic acid during drug loading. Consequently, its releasing performance was very poor. For BC:HC blend films, ascorbic acid loading/releasing performance was balanced by water swellability, which was controlled using blending formulation and coating. Another advantage of BC films and BC:HC blend films was that they were able to maintain active ascorbic acid for a long period of time, probably due to the presence of plenty of BC hemiacetal reducing ends (protective group). Full article

Oxidized sucrose is a non-formaldehyde crosslinking agent with many applications in polymer crosslinking and modification, such as in the preparation of starch films and protein films. However, research on the structure of oxidized sucrose is lacking. In this paper, oxidized sucrose was synthesized through selective oxidation of sodium periodate. By LC-MS, FTIR, TGA, NMR, and HRMS analyses, it was shown that oxidized sucrose existed in the form of a hydrate, and the tetraaldehyde oxidized sucrose could isomerize into the form of two six-membered hemiacetal rings. The structure of oxidized sucrose was also verified by theoretical calculations. Furthermore, the diffusional properties of oxidized sucrose were investigated by the rolling-film method. Finally, it was found that oxidized sucrose used as a crosslinking agent could effectively improve the wrinkle recovery performance of cotton fabrics. Full article

Synthesis of the first representative of a 5-formyl-1H-1,2,3-triazole-4-carboxylic acids series – 1-(4-ethoxyphenyl)-5-formyl-1H-1,2,3-triazole-4-carboxylic acid was performed. The 1-azido-4-ethoxybenzene was chosen as a starting reagent in a two-step synthesis, which reacted with the ethyl 4,4-diethoxy-3-oxobutanoate under base catalysis to form ethyl 5-(diethoxymethyl)-1-(4-ethoxyphenyl)-1H-1,2,3-triazole-4-carboxylate with protected formyl and acid groups. By the subsequent saponification of the ester group and removing of acetal protection, the target 1-(4-ethoxyphenyl)-5-formyl-1H-1,2,3-triazole-4-carboxylic acid was obtained. It has been found that the free acid form predominated in the solution under its cyclic 6-hydroxy-1,6-dihydro-4H-furo[3,4-d][1,2,3]triazol-4-one tautomer. According to ¹H NMR, cyclic hemiacetal is about 20%. Full article