Search Results (25)

Ixora chinensis Lam. has traditionally been used to treat conditions such as acne, high blood pressure, bleeding, tuberculosis, and rheumatism. This study aimed to investigate the methanolic extract of I. chinensis leaves to determine their bioactive compounds and evaluate their effects on both central and peripheral pain using in vivo and in silico approaches. The GC-MS analysis revealed 41 phytochemicals, including 14 phenolics, 4 esters, 12 terpenoids, 8 alkaloids, and 3 sulfur-containing compounds. In the glucose tolerance test, both the chloroform-soluble fraction (CF) and n-hexane fraction (NHF) exhibited p < 0.05 reductions in blood glucose levels at a dosage of 400 mg/kg with decreases of 51.94% and 46.63%, respectively, compared to the positive control (64.02%). The central analgesic evaluation showed significant (p < 0.001) enhancements in tail-flick latency for the fraction (184.94%) and CF (170.51%) following 90 min. In the pain relief assay, NHF showed inhibition (64.33%, p < 0.001) followed by an aqueous fraction (57.35%). These pharmacological findings were supported by in silico analysis. Concerning activity, 5-(dimethylamino)-1- acid phenyl ester (−8.9 kcal/mol) and 9,9-dimethyl-9H-fluoren-3-ol (−8.4 kcal/mol) displayed the strongest binding affinity to AMPK. Additionally, 2,3-diphenyl-2-cyclopropen-1-one exhibited favorable interactions with α-amylase (−8.0 kcal/mol) and α-glucosidase (−8.3 kcal/mol). Similarly, the central analgesic effect correlated with the strong μ-opioid receptor affinity of s-Triazine, 2-amino-4-(piperidinomethyl)-4-piperidino (−8.8 kcal/mol). N-Methyl-N-(4-toluenesulfonyl)-benzamide (−8.6 kcal/mol) and s-Triazine derivative (−8.9 kcal/mol) demonstrated notable COX-1 and COX-2 inhibition potential. Overall, the findings indicate I. chinensis leaves as a promising source of bioactive compounds with significant antihyperglycemic and analgesic properties. Full article

A series of 3-azabicyclo[3.1.0]hexanes and cyclopropa[a]pyrrolizidines spiro-fused to acenaphthylene-1(2H)-one and aceanthrylene-1(2H)-one frameworks have been studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), melanoma (Sk-mel-2), osteosarcoma (U2OS), as well as murine melanoma (B16) cell lines. Using confocal microscopy, it was found that cultivation with the tested spiro-fused compounds led to the disappearance of stress fibers (granular actin was distributed diffusely in the cytoplasm in up to 56% of treated cells) and decrease in filopodia-like deformations (up to 69% after cultivation), which indirectly suggests a decrease in cell motility. The human melanoma cell line scratch test showed that these cells lose their ability to move after cultivation with the tested spiro-fused compounds and do not fill the scratched strip. This was also supported by docking simulations with actin-related targets (PDB ID: 8DNH, 2Q1N). Using flow cytometry, the impact on the mitochondrial membrane potential showed that the tested compounds led to a significant increase in the number of cells with decreased mitochondrial membrane potential from 10% for the control up to 55–80% for the cyclopropa[a]pyrrolizidine adducts. The obtained results support the antitumor effect of the tested spiro-compounds and encourage the extension of the study in order to improve their anticancer activity as well as reduce their toxicological risks. Full article

Fruits are an important source of a healthy diet due to their essential nutrients for daily intake. Melon is known as a significant fruit crop of the Cucurbitaceae family based on its various dietary benefits, but its shelf life needs to be maintained for long-term usage. 1-Methylcyclopropene (1-MCP) is a cyclopropene-derived synthetic plant growth regulator (PGR) that is used for significantly delaying the ripening process and maintaining the shelf life of climacteric fruits during storage. In this study, freshly harvested melon fruits were fumigated with various concentrations (1.0 µL·L⁻¹, 2.0 µL·L⁻¹, and 3.0 µL·L⁻¹) of 1-MCP treatment for 12 h (h) and stored at low temperature (8 ± 1 °C) for 30 days (d). The obtained results showed that 1-MCP fumigation coupled with low-temperature treatment maintains the postharvest shelf life of melon fruit. It was noticed that the increase in color hue (a* (red/green), b* (blue/yellow), L* (lightness)) was slowed down and the external fresh color was effectively maintained. At the same time, the firmness, soluble solids, titratable acids (TAs), and vitamin C (VC) content seemed to be maintained at a high level; weight loss and cell permeability were reduced; respiratory intensity and ethylene emission were inhibited; and the accumulation of superoxide anions and malondialdehyde (MDA) was also reduced. In addition, an upsurge in the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) was noticed in melon fruits under the combined treatment of 1-MCP and low-temperature storage as compared with the control group (CK, without treatment), indicating that 1-MCP treatment can effectively enhance the antioxidant metabolism of melon fruits during storage. Overall, we can recommend that the 3.0 µL·L⁻¹ concentration of 1-MCP had the best effect on maintaining the internal and external quality of sweet melon fruit during storage. Full article

Wuyi Rock tea (WRT), originating from the northern region of Fujian province, has a good reputation for its distinctive Yan flavor and floral–fruity aroma. The aroma quality, an essential element of the Yan flavor, undergoes various changes during the manufacturing process of WRT. To enhance the understanding of the formation patterns of WRT aroma and its influence on the flavor quality of WRT, we utilized both manufactured WRT (Rougui tea) and primary tea as materials. Utilizing a sensory evaluation, detection of volatile compounds, and multivariate statistical analysis, we identified and characterized the distinctive volatile components present in WRT. The sensory evaluation and radar chart analysis revealed that the primary tea exhibited a strong and lasting aroma, along with a mellow taste and a prominent Yan flavor. Through gas chromatography time-of-flight mass spectrometry (GC-TOF MS), a total of 251 volatile compounds were identified. The odor activity value (OAV) was calculated to identify key aroma-active compounds in the primary tea. The results indicated that a total of 14 compounds had an OAV greater than 1.0, including (2-nitroethyl) benzene, indole, and geranylacetone. These compounds exhibited floral and fruity aroma attributes. They primarily formed and accumulated during the latter stages of WRT. Using a partial least squares discrimination analysis (PLS-DA) combined with a variable importance in projection (VIP) score greater than 1.0 as a criterion, a total of 89 compounds were identified. Furthermore, out of the selected compounds, 15 types, including geraniol, 1-nonanol, and 1-butyl-2-ethyl-cyclopropene, were found to exclusively exist during the enzymatic manufacturing stages, particularly during the intermediate and later phases of the turn-over process (the last-three-times turn-over treatments), exhibiting predominantly floral and sweet fragrances. In contrast, during the non-enzymatic stages, only four compounds, such as pentanoic acid and phenylmethyl ester, were detected, exhibiting a fruity aroma profile. These volatile compounds significantly influenced the quality attributes of the final tea product, resulting in strong and lasting characteristics, particularly marked by a pronounced floral and fruity aroma. This study revealed how the aroma quality in WRT is developed and pinpointed possible volatile compounds that react to post-harvest treatments, thereby offering valuable insights relating to the intelligent production strategies of WRT. Full article

1-Methyl cyclopropene (1-MCP) is known as an ethylene antagonist, yet its mechanisms in regulating photosynthetic electron transport and energy dissipation in chrysanthemum under heat stress are not well understood. Here, the chlorophyll a fluorescence and modulated 820 nm reflection transients were analyzed in heat-tolerant and heat-sensitive chrysanthemum plants. This study demonstrates that 1-MCP pre-treatment helps maintain the net photosynthetic rate (P_n) and the reaction center activity of photosystems I and II (PSI and PSII) during heat stress. Specifically, 1-MCP treatment significantly increases the fraction of active oxygen-evolving complex (OEC) centers and reduces relative variable fluorescence intensity at the J step (V_J) as well as the efficiency of electron transfer at the PSI acceptor side (δ_Ro). These effects mitigate damage to the photosynthetic electron transport chain. Additionally, 1-MCP-treated plants exhibit decreased quantum yield of energy dissipation (φ_Do) and reduced energy flux per reaction center (DI_o/RC). Overall, 1-MCP enhances light utilization efficiency and excitation energy dissipation in the PSII antennae, alleviating heat stress-induced damage to PSI and PSII structures and functions. This study not only advances our understanding of 1-MCP’s regulatory role in photosynthetic processes under heat stress but also provides a basis for using exogenous substances to improve chrysanthemum heat resistance. Full article

Background: A series of spiro-fused heterocyclic compounds containing cyclopropa[a]pyrrolizidine-2,3′-oxindole and 3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole frameworks were synthesized and studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), acute T cell leukemia (Jurkat), melanoma (Sk-mel-2) and breast cancer (MCF-7) as well as mouse colon carcinoma (CT26) cell lines. Methods: Cell proliferation was evaluated in vitro by MTS assay. Confocal microscopy was used to study actin cytoskeleton structure and cell motility. Cell cycle analysis was evaluated by flow cytometry. Results: It was found that compounds 4, 8, 18 and 24 showed antiproliferative activity against the Jurkat, K-562, HeLa and Sk-mel-2 cell lines with IC₅₀ ranging from 2 to 10 μM (72 h). Evaluation of the impact on cell cycle progression showed that the tested compounds achieved significant cell-cycle perturbation with a higher accumulation of cells in the SubG1 and G0/G1 phases of the cell cycle, in comparison to the negative control. I Incubation with tested compounds led to the disappearance of stress fibers (granular actin was distributed diffusely in the cytoplasm in up to 38% of treated HeLa cells) and changes in the number of filopodia-like deformations (reduced from 93% in control cells to 64% after treatment). The impact on the Sk-mel-2 cell actin cytoskeleton structure was even greater: granular actin was distributed diffusely in the cytoplasm in up to 90% of treated cells while the number of filopodia-like deformations was reduced by up to 23%. A scratch test performed on the human melanoma cell line showed that these cells did not fill the scratched strip and lose their ability to move under treatment. Conclusions: The obtained results support the antitumor effect of the tested spiro-compounds and encourage the extension of this study in order to improve their anticancer activity as well as reduce their toxicological risks. Full article

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C−H, N−H, O−H, S−H, and Si−H bonds. Typically, reactions from diazo compounds are catalyzed by transition metals with various ligands that modulate the capacity and selectivity of the catalyst. These ligands can modify and enhance chemoselectivity in the substrate, regioselectivity and enantioselectivity by reflecting these preferences in the products. Porphyrins have been used as catalysts in several important reactions for organic synthesis and also in several medicinal applications. In the chemistry of diazo compounds, porphyrins are very efficient as catalysts when complexed with low-cost metals (e.g., Fe and Co) and, therefore, in recent years, this has been the subject of significant research. This review will summarize the advances in the studies involving the field of diazo compounds catalyzed by metalloporphyrins (M−Porph, M = Fe, Ru, Os, Co, Rh, Ir) in the last five years to provide a clear overview and possible opportunities for future applications. Also, at the end of this review, the properties of artificial metalloenzymes and hemoproteins as biocatalysts for a broad range of applications, namely those concerning carbene-transfer reactions, will be considered. Full article

We evaluate the accuracy of CCSD(T) and density functional theory (DFT) methods for the calculation of equilibrium rotational constants ($A_e$, $B_e$, and $C_e$) for four experimentally detected low-lying C${}_5$H${}_2$ isomers (ethynylcyclopropenylidene (2), pentatetraenylidene (3), ethynylpropadienylidene (5), and 2-cyclopropen-1-ylidenethenylidene (8)). The calculated rotational constants are compared to semi-experimental rotational constants obtained by converting the vibrationally averaged experimental rotational constants ($A_0$, $B_0$, and $C_0$) to equilibrium values by subtracting the vibrational contributions (calculated at the B3LYP/jun-cc-pVTZ level of the theory). The considered isomers are closed-shell carbenes, with cumulene, acetylene, or strained cyclopropene moieties, and are therefore highly challenging from an electronic structure point of view. We consider both frozen-core and all-electron CCSD(T) calculations, as well as a range of DFT methods. We find that calculating the equilibrium rotational constants of these C${}_5$H${}_2$ isomers is a difficult task, even at the CCSD(T) level. For example, at the all-electron CCSD(T)/cc-pwCVTZ level of the theory, we obtain percentage errors ≤0.4% ($C_e$ of isomer 3, $B_e$ and $C_e$ of isomer 5, and $B_e$ of isomer 8) and 0.9–1.5% ($B_e$ and $C_e$ of isomer 2, $A_e$ of isomer 5, and $C_e$ of isomer 8), whereas for the $A_e$ rotational constant of isomers 2 and 8 and $B_e$ rotational constant of isomer 3, high percentage errors above 3% are obtained. These results highlight the challenges associated with calculating accurate rotational constants for isomers with highly challenging electronic structures, which is further complicated by the need to convert vibrationally averaged experimental rotational constants to equilibrium values. We use our best CCSD(T) rotational constants (namely, ae-CCSD(T)/cc-pwCVTZ for isomers 2 and 5, and ae-CCSD(T)/cc-pCVQZ for isomers 3 and 8) to evaluate the performance of DFT methods across the rungs of Jacob’s Ladder. We find that the considered pure functionals (BLYP-D3BJ, PBE-D3BJ, and TPSS-D3BJ) perform significantly better than the global and range-separated hybrid functionals. The double-hybrid DSD-PBEP86-D3BJ method shows the best overall performance, with percentage errors below 0.5% in nearly all cases. Full article

Oncological diseases are one of the most common public health problems and the second leading cause of death after cardiovascular disease. Natural products or synthetic compounds derived from natural products continue to be excellent sources for new drug candidates. Recent advances in synthesis of complex heterocyclic systems have led to significant increase in interest in development of efficient methods for synthesis of thereof as potential drugs or biological probes. Oxindole, azabicyclohexane and pyrrolizine units are known heterocyclic motifs that form the core of a large family of alkaloid natural products with strong bioactivity profiles. Series of heterocyclic compounds containing 3-spiro[3-azabicyclo[3.1.0]hexane]oxindole framework have been studied for their antiproliferative activity against K562, Jurkat, HeLa, and CT26 cell lines. These spiro-fused adducts are readily available via one-pot three-component 1,3-dipolar cycloaddition reactions of cyclopropenes and azomethine ylides (generated in situ from amino acids and oxindoles). In agreement with DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Using confocal microscopy, we found that actin filaments disappeared and granular actin was distributed diffusely in the cytoplasm in up to 40% of treated cells. In addition, we discovered that the number of cells with filopodium-like membrane protrusions was significantly reduced after treatment with some of the tested compounds (from 92% in control cells up to 36% after treatment). The obtained results support the antitumor effect of the studied compounds and encourage the extension of the study in order to improve the anticancer activity and reduce the toxicological risks of the obtained compounds. Full article

The possibility of generating azomethine ylides from 11H-benzo[4,5]imidazo[1,2-a]indol-11-one and amino acids is shown for the first time. Based on the cycloaddition reactions of these azomethine ylides with cyclopropenes and maleimides, cyclopropa[a]pyrrolizines, 3-azabicyclo[3.1.0]hexanes, and pyrrolo[3,4-a]pyrrolizines spiro-fused with a benzo[4,5]imidazo[1,2-a]indole fragment were synthesized. Spirocyclic compounds were obtained in moderate to good yields, albeit with poor diastereoselectivity. Density functional theory calculations were performed to obtain an insight into the mechanism of the 1,3-dipolar cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived azomethine ylides to cyclopropenes. The cytotoxic activity of some of the obtained cycloadducts against the human erythroleukemia (K562) cell line was evaluated in vitro by MTS-assay. Full article

Enantiomerically enriched cyclopropyl ethers, amines, and cyclopropylazole derivatives possessing three stereogenic carbon atoms in a small cycle are obtained via the diastereoselective, formal nucleophilic substitution of chiral, non-racemic bromocyclopropanes. The key feature of this methodology is the utilization of the chiral center of the cyclopropene intermediate, which governs the configuration of the two adjacent stereocenters that are successively installed via 1,4-addition/epimerization sequence. Full article

A series of heterocyclic compounds containing spirofused barbiturate and 3-azabicyclo[3.1.0]hexane frameworks have been studied as potential antitumor agents. Antiproliferative activity of products was screened in human erythroleukemia (K562), T lymphocyte (Jurkat), and cervical carcinoma (HeLa) as well as mouse colon carcinoma (CT26) and African green monkey kidney epithelial (Vero) cell lines. The most effective among the screened compounds show IC₅₀ in the range from 4.2 to 24.1 μM for all tested cell lines. The screened compounds have demonstrated a significant effect of the distribution of HeLa and CT26 cells across the cell cycle stage, with accumulation of cells in SubG1 phase and induced apoptosis. It was found, using a confocal microscopy, that actin filaments disappeared and granular actin was distributed diffusely in the cytoplasm of up to 90% of HeLa cells and up to 64% of CT26 cells after treatment with tested 3-azaspiro[bicyclo [3.1.0]hexane-2,5′-pyrimidines]. We discovered that the number of HeLa cells with filopodium-like membrane protrusions was reduced significantly (from 91% in control cells to 35%) after treatment with the most active compounds. A decrease in cell motility was also noticed. Preliminary in vivo experiments on the impact of the studied compounds on the dynamics of CT26 tumor growth in Balb/C mice were also performed. Full article

As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed advances, copper carbenes are versatile and reactive intermediates that can mediate a variety of transformations, which have attracted much attention in the past decades. The present review summarizes two different reaction models that take place between a copper carbene intermediate and alkyne species, including the cross-coupling reaction of copper carbene intermediate with terminal alkyne, and the addition of copper carbene intermediate onto the C–C triple bond. This article will cover the profile from 2010 to 2021 by placing emphasis on the detailed catalytic models and highlighting the synthetic applications offered by these practical and mild methods. Full article

The raspberry (Rubus idaeus) is an important fruit crop; however, its accelerated softening is a critical postharvest problem, even at low temperatures. Its softening has been partially associated with the endogenous production of ethylene from the receptacle during ripening. To understand the relationship between ethylene production and fruit quality at the beginning of the ripening process, the physiological and quality parameters were evaluated during the ripening of the ‘Heritage’ cultivar. Two storage assays, at 0 °C and 10 °C, were carried out with independent groups of fruits attached to their receptacle at the white stage of fruit development. The treatments included fruit treated with ethylene (1000 ppb) and ethylene perception inhibitor 1-methyl cyclopropene (1-MCP, 1600 ppb) and a control treatment. During ripening, the endogenous production of ethylene in whole fruit was negatively correlated with the loss of firmness. During storage at 0 °C, firmness and ethylene production only decreased by the effect of storage time, with a firmness near 1.5 Newtons at 16 days. On the other hand, the storage at 10 °C showed a delay in the firmness loss and lower ethylene production of the fruit treated with 1-MCP, compared to the control and ethylene-treated fruit. In addition, these two last assays showed a firmness close to 1 Newton at 5 days. No significant differences were observed in the total soluble solids content and titratable acidity between the three treatments at the two storage temperatures. The results during ripening and storage at 10 °C indicate that the loss of the fruit’s firmness is positively related to the endogenous ethylene production of the whole fruit from 1 to 5 days of storage. Future assays should be performed to determine the role of ethylene in raspberry ripening. Full article

The gas-phase basicity of nitriles can be enhanced by a push–pull effect. The role of the intercalated scaffold between the pushing group (electron-donor) and the pulling (electron-acceptor) nitrile group is crucial in the basicity enhancement, simultaneously having a transmission function and an intrinsic contribution to the basicity. In this study, we examine the methylenecyclopropene and the N-analog, cyclopropenimine, as the smallest cyclic π systems that can be considered for resonance propagation in a push–pull system, as well as their derivatives possessing two strong pushing groups (X) attached symmetrically to the cyclopropene scaffold. For basicity and push–pull effect investigations, we apply theoretical methods (DFT and G2). The effects of geometrical and rotational isomerism on the basicity are explored. We establish that the protonation of the cyano group is always favored. The push–pull effect of strong electron donor X substituents is very similar and the two π-systems appear to be good relays for this effect. The effects of groups in the two cyclopropene series are found to be proportional to the effects in the directly substituted nitrile series X–C≡N. In parallel to the basicity, changes in electron delocalization caused by protonation are also assessed on the basis of aromaticity indices. The calculated proton affinities of the nitrile series reported in this study enrich the gas-phase basicity scale of nitriles to around 1000 kJ mol⁻¹. Full article