Fe3O4@SiO2@NTMPThio-Cu: a sustainable and eco-friendly approach for the synthesis of heterocycle derivatives using a novel dendrimer template nanocatalyst.

In this research, Fe3O4@SiO2@NTMPThio-Cu was introduced as a novel and green heterogeneous nanocatalyst with a dendrimer template that is environmentally friendly and reusable based on Fe3O4@SiO2. In this way, magnetic silica nanoparticles were first modified with cyanuric chloride, followed by melamine and thiosemicarbazide, and ultimately, it's decorated with the cost-effective metal copper. The synthesized nanocatalyst was characterized by various analyses such as FT-IR, XRD, SEM, TGA, and EDX. The efficiency of Fe3O4@SiO2@NTMPThio-Cu was measured in one-pot synthesis of xanthene and spirooxindole-pyran derivatives under mild solvent-free conditions. High efficiency, excellent yield of products, mild reaction conditions, simple operation, no use of toxic organic solvents, and reusability of this catalyst increase the attractiveness of this technique for large-scale environmentally friendly operations.

A Chemically Robust 2D Ni-MOF as an Efficient Heterogeneous Catalyst for One-Pot Synthesis of Therapeutic and Bioactive 2-Amino-3-Cyano-4H-Pyran Derivatives.

Despite possessing numerous catalytic advantages of MOFs, developing 2D frameworks having excellent chemical stability along with new catalytic properties, remains a grand challenge. Herein, by employing a mixed ligand synthetic approach, we have constructed a 2D Ni-MOF, IITKGP-52, which exhibits excellent framework robustness in open air, water, as well as over a wide range of pH solutions (2-12). Benefitting from its robustness and abundant Lewis acidic open metal sites, IITKGP-52 is explored in catalyzing the heterogeneous three-component condensation reaction for the tandem synthesis of bioactive 2-amino-3-cyano-4H-pyran derivatives with low catalytic loading, greater compatibility for a wide range of substrates, excellent recyclability and superior catalytic efficiency than the previously employed homo and heterogeneous systems. IITKGP-52 inaugurates the employment of MOF-based catalysts for one-pot synthesis of therapeutic and bioactive 2-amino-3-cyano-4H-pyran derivatives.

Microbial synthesis of anthocyanins and pyranoanthocyanins: current bottlenecks and potential solutions.

Anthocyanins (ACNs) are secondary metabolites found in plants. Due to their impressive biological activities, ACNs have gained significant popularity and extensive application within the food, pharmaceutical, and nutraceutical industries. A derivative of ACNs: pyranoanthocyanins (PACNs) possesses more stable properties and interesting biological activities. However, conventional methods for the production of ACNs, including chemical synthesis and plant extraction, involve organic solvents. Microbial synthesis of ACNs from renewable biomass, such as amino acids or flavonoids, is considered a sustainable and environmentally friendly method for large-scale production of ACNs. Recently, the construction of microbial cell factories (MCFs) for the efficient biosynthesis of ACNs and PACNs has attracted much attention. In this review, we summarize the cases of microbial synthesis of ACNs, and analyze the bottlenecks in reconstructing the metabolic pathways for synthesizing PACNs in microorganisms. Consequently, there is an urgent need to investigate the mechanisms behind the development of MCFs for PACNs synthesis. Such research also holds significant promise for advancing the production of food pigments. Meanwhile, we propose potential solutions to the bottleneck problem based on metabolic engineering and enzyme engineering. Finally, the development prospects of natural food and biotechnology are discussed.

Identification of Yellow Advanced Glycation End Products in Human Skin.

Skin yellowness is a hallmark of dull or unhealthy skin, particularly among Asians. Previous research has indicated a link between skin glycation and skin yellowness. However, the specific glycated chemicals contributing to yellowish skin appearance have not been identified yet. Using HPLC-PDA-HRMS coupled with native and artificially glycated human epidermal explant skin, we identified intensely yellow colored glycated chromophores "(1R, 8aR) and (1S, 8aR)-4-(2-furyl)-7-[(2-furyl)-methylidene]-2-hydroxy-2H,7H,8AH-pyrano-[2,3-B]-pyran-3-one" (abbreviated as AGEY) from human skin samples for the first time. The abundance of AGEY was strongly correlated with skin yellowness in the multiple skin explant tissues. We further confirmed the presence of AGEY in cultured human keratinocytes and 3D reconstructed human epidermal (RHE) models. Additionally, we demonstrated that a combination of four cosmetic compounds with anti-glycation properties can inhibit the formation of AGEY and reduce yellowness in the RHE models. In conclusion, we have identified specific advanced glycation end products with an intense yellow color, namely AGEY, in human skin tissues for the first time. The series of study results highlighted the significant contribution of AGEY to the yellow appearance of the skin. Furthermore, we have identified a potential cosmetic solution to mitigate AGEY formation, leading to a reduction in yellowness in the in vitro RHE models.

Metabolites isolated from Penicillium HDS-Z-1E, an endophytic fungal strain isolated from Taxus cuspidata and their activation effect of catalase.

Objective: To study the compounds isolated from Penicillium HDS-Z-1E, an endophytic fungal strain isolated from Taxus cuspidata and their activation effect of catalase (CAT). Methods: The chemical constituents were isolated from Penicillium HDS-Z-1E, by using silica gel, Sephadex LH-20 and HPLC. The structural elucidations of five metabolites were elucidated on the basis of spectroscopic including 1H-NMR, 13C-NMR, HMBC and HSQC. Their activation sites of catalase have been investigated by molecular docking. Results: Five metabolites, compounds (1-5) were isolated from Penicillium HDS-Z-1E and identified as 4-hydroxy-4-methyltetrahydro-2H-pyran-2-one (1), 4-hydroxymethyl-5, 6-dihydro-pyran-2-one (2), 5, 6-dihydro-2-oxo-2H-pyran-4-carboxylic (3), N-acetyl-hydrazinobenzoic acid (4), and methyl 2-(2, 5-dihydroxyphenyl) acetate (5). Conclusion: Compound 3 is a new compound. Compounds 3 and 4 may have potential activators of catalase, providing a theoretical basis for the development of CAT activators.

5-Oxo-dihydropyranopyran derivatives as anti-proliferative agents; synthesis, biological evaluation, molecular docking, MD simulation, DFT, and in-silico pharmacokinetic studies.

A series of ethyl 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[4,3-b]pyran-3-carboxylate derivatives (4a-j) bearing different substitutions on the C4-phenyl ring was synthesized. The anti-proliferative activity of all the synthesized compounds was assessed against two human cancer-cell lines, including SW-480 and MCF-7, by using MTT method. Derivatives 4g, 4i, and 4j, possessing 4-NO2, 4-Cl, and 3,4,5-(OCH3)3 substitutions, were found to be the most potent compounds against both cell lines. The obtained IC50 values for 4g, 4i, and 4j were 34.6, 35.9, and 38.6 µM against SW-480 cells and 42.6, 34.2, and 26.6 µM against MCF-7 cells, respectively. Evaluation of the free radical scavenging potential of the compounds against DPPH radicals showed the highest result for compound 4j with an EC50 value of 580 µM. Molecular docking studies revealed the compounds were well accommodated within the binding site of cyclin-dependent kinase-2 (CDK2) with binding energies comparable to those of DTQ (the co-crystallized inhibitor) and BMS-265246 (a well-known CDK2 inhibitor). Molecular dynamics simulation studies confirmed the interactions and stability of the 4g-CDK2 complex. All derivatives, except 4g, were predicted to comply with the drug-likeness rules. Compound 4j may be proposed as an anti-cancer lead candidate for further studies due to the promising findings from in-silico pharmacokinetic studies, such as high GI absorption, not being a P-gp substrate, and being a P-gp inhibitor. Density functional theory (DFT) analysis was performed at the B3LYP/6-311++G (d,p) level of theory to examine the reactivity or stability descriptors of 4d, 4g, 4i, and 4j derivatives. The highest value of energy gap between HOMO and LUMO and thermochemical parameters were obtained for 4i and 4j.

Near-infrared fluorescent indolizine-dicyanomethylene-4H-pyran hybrids for viscosity imaging in living cells.

The development of near-infrared organic fluorescent dyes with tunable emission profiles is highly required in the field of biological sensing and imaging. In this paper, we designed and synthesized two organic fluorescent dyes, DCM-1 and DCM-2, through the hybridization of indolizine and dicyanomethylene-4H-pyran skeleton. These two compounds show near-infrared fluorescence with emission maximum approximately at 640 and 680 nm, respectively. Notably, both DCM-1 and DCM-2 have specific responses to viscosity without being interfered by biological relevant species. Cell experiments demonstrate that DCM-1 and DCM-2 can detect dynamic changes in viscosity within living cells, suggesting their potential applications in chemical biology research.

Synthesis, Antimicrobial Evaluation, DFT, and Molecular Docking Studies of Pyrano [4,3-b] Pyranone and Pyrano[2,3-b]Pyridinone Systems.

Dehydroacetic acid (DHA) was utilized as a fundamental precursor in the synthesis of novel pyrano [4,3-b] pyran and pyrano [2,3-b] pyridine systems. Whereas, a new series of fused polyheteronuclear systems was achieved through the reaction of DHA with active methylene compounds such as malononitrile and pyrazolone. Whereas, the treatment of DHA 1 with cyclic ketones involving cyclohexanone and cyclododecanone afforded annulated tricyclic system 6 and spiro hybrid molecule 7. Also, the reaction of DHA 1 with cyanoacetamide derivatives 8 and 11 yielded their corresponding novel pyrano [2,3-b] pyridine-6-carbonitrile frameworks 9 and 12, respectively. Also, in silico predictive theoretical molecular docking studies for bioactive synthesized scaffolds against both HER2 and 6BBP displayed an optimistic result for compounds 2 b, 5, 9, and 12 highlighting their expediency as up-and-coming candidates for future preclinical trials. Additionally, all compounds were assessed as antibacterial agents against various types of four candidates of bacteria in the presence of ampicillin as a reference. Notably, compounds 6, 7, and 12 showed promising antibacterial potential against Bacillus subtilis with activity indexes (69.6, 91.3, and 82.6 %), respectively.

1-Ethyl-3,3-di-methyl-spiro-[indoline-2,8'-phenaleno[1,9-fg]chromene].

The title pyrene-fused spiro-pyran derivative, C30H25NO, crystallizes with two mol-ecules in the asymmetric unit with dihedral angles between their fused-ring sub units of 76.20 (8) and 89.38 (9)°. In the crystal, weak C-H⋯π inter-actions link the mol-ecules into a three-dimensional network.

Immunosuppressive effects of the mycotoxin patulin in macrophages.

Patulin (PAT) is a fungi-derived secondary metabolite produced by numerous fungal species, especially within Aspergillus, Byssochlamys, and Penicillium genera, amongst which P. expansum is the foremost producer. Similar to other fungi-derived metabolites, PAT has been shown to have diverse biological features. Initially, PAT was used as an effective antimicrobial agent against Gram-negative and Gram-positive bacteria. Then, PAT has been shown to possess immunosuppressive properties encompassing humoral and cellular immune response, immune cell function and activation, phagocytosis, nitric oxide and reactive oxygen species production, cytokine release, and nuclear factor-κB and mitogen-activated protein kinases activation. Macrophages are a heterogeneous population of immune cells widely distributed throughout organs and connective tissue. The chief function of macrophages is to engulf and destroy foreign bodies through phagocytosis; this ability was fundamental to his discovery. However, macrophages play other well-established roles in immunity. Thus, considering the central role of macrophages in the immune response, we review the immunosuppressive effects of PAT in macrophages and provide the possible mechanisms of action.

Green Chemistry and In silico Techniques for Synthesis of Novel Pyranopyrazole and Pyrazolo-pyrano-pyrimidine Derivatives as Promising Antifungal Agents.

BACKGROUND: Every year Invasive Fungal Infections (IFI) are globally affecting millions of people. Candida albicans and Aspergillus niger have been reported as the most infectious and mortality-inducing fungal strains among all pathogenic fungi. AIMS & OBJECTIVES: To tackle this problem in the current study Pyranopyrazoles and Pyrazolopyrano- pyrimidine derivatives were developed using molecular hybridization, green chemistry and one-pot multicomponent reaction. MATERIALS AND METHODS: In the present work, New Chemical entities (NCE's) were developed on the basis of Structure activity relationship. All designed NCE's were screened for ADMET studies using the QikProp module of Schrodinger software. NCE's with zero violations were further docked on the crystal structure of 14α demethylase, cytochrome P450 and thymidine synthase (PDB ID: 5V5Z, 7SHI, 1BID). Selected molecules were synthesized using green chemistry techniques and evaluated for in vitro antifungal activity against Candida albicans and Aspergillus niger. RESULTS AND DISCUSSION: Designed NCE's (B1-12 and C1-11) showed favorable results in ADMET studies. In the docking study six compounds from series-B and five molecules from series- C showed good dock score and binding interaction when compared with the standard drugs. Compounds B-3 and C-4 showed the highest zone of inhibition activity against Candida albicans, where as B-1 and C-3 had shown highest zone of inhibition activity against Aspergillus niger. CONCLUSION: Bicyclic ring (series B) showed better activity as compare to fused tricyclic ring (series C).

Design, synthesis, and molecular dynamics simulation studies of some novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors.

A novel series of kojic acid fused 2-amino-3-cyano-4H-pyran derivatives were synthesized via a multicomponent reaction involving kojic acid, benzyloxy benzaldehyde, and malonitrile as tyrosinase inhibitors. Subsequently, the structures of the compounds were characterized using FT-IR, 1H-, and 13C-NMR spectroscopic analyses. The designed compounds fall into three series: (1) 4-benzyloxy-phenyl kojopyran 6a-e, (2) 3-benzyloxy- phenyl kojopyran derivatives 6f-j, and (3) 4-benzyloxy-3-methoxy-phenyl kojopyran derivative 6 k-o. The assessment of tyrosinase inhibition activity was conducted using L-Dopa as the substrate. Among synthesized compounds, 2-amino-4-(4-((4-fluorobenzyl)oxy)phenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (6b) demonstrated the highest antityrosinase activity with a competitive inhibition pattern (IC50 = 7.69 ± 1.99 µM) as compared to the control agent kojic acid (IC50 = 23.64 ± 2.56 µM). Since compound 6b was synthesized as a racemic mixture, in silico studies were performed for both R and S enantiomers. The R- enantiomer showed critical interactions compared with the S-enantiomer. Specifically, it established hydrogen bonds and hydrophobic interactions with crucial and highly conserved amino acids within the enzyme's binding site in the target protein. Moreover, the molecular dynamics simulations revealed that compound 6b demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run. The drug-like and ADMET properties predictions showed an acceptable profile for compound 6b. Thus, it can serve as a drug candidate to develop more potent antityrosinase agents due to its low toxicity and its high inhibition activity.

Antiproliferative polyketides from fungus Xylaria cf. Longipes SWUF08-81 in different culture media.

Bioactive compounds from the wood-decay fungus Xylaria cf. longipes SWUF08-81, cultivated in three different culture media (GM, YM and PDB), were isolated. Their structures and stereochemistry were deduced from spectroscopic and MS data analysis, together with quantum chemical calculations of 13C NMR chemical shifts and electronic circular dichroism (ECD) spectra. Five undescribed polyketides including dibenzofuran (1), mellein (2), dihydroisocoumarin (15), and two pyrans (16, 17), together with twenty-three compounds were determined. Compounds 18 and 20 were significantly toxic against cancer cell lines (HCT116, HT29, MCF-7 and HeLa) based on the MTT assay. Quantification by HPLC showed that 18 was produced three-fold higher in the broth of PDB than YM. These studies showed that the production of different compounds were primarily dependent on nutrition sources and it has given a starting point for the growth optimization conditions for the scaling up of bioactive compounds production.

Activatable Near-Infrared Versatile Fluorescent and Chemiluminescent Dyes Based on the Dicyanomethylene-4H-pyran Scaffold: From Design to Imaging and Theranostics.

Activatable fluorescent and chemiluminescent dyes with near-infrared emission have indispensable roles in the fields of bioimaging, molecular prodrugs, and phototheranostic agents. As one of the most popular fluorophore scaffolds, the dicyanomethylene-4H-pyran scaffold has been applied to fabricate a large number of versatile activatable optical dyes for analytes detection and diseases diagnosis and treatment by virtue of its high photostability, large Stokes shift, considerable two-photon absorption cross-section, and structural modifiability. This review discusses the molecular design strategies, recognition mechanisms, and both in vitro and in vivo bio-applications (especially for diagnosis and therapy of tumors) of activatable dicyanomethylene-4H-pyran dyes. The final section describes the current shortcomings and future development prospects of this topic.

6-Pentyl-2H-pyran-2-one from Trichoderma erinaceum Is Fungicidal against Litchi Downy Blight Pathogen Peronophythora litchii and Preservation of Litchi.

The postharvest losses of litchi caused by litchi downy blight are considerably high. We identified a natural antifungal volatile pyrone, 6-pentyl-2H-pyran-2-one (6PP), synthesized by Trichoderma erinaceum LS019-2 and investigated as biocontrol for litchi downy blight and preservation. 6PP significantly inhibited the growth and sporangial germination of Peronophythora litchii, the causal agent of litchi downy blight, and caused severe cellular and intracellular destructions, as evidenced by electron microscopic analysis. Furthermore, in the treatment, the fruit kept better color, higher weight, and antioxidant activity, so it can maintain freshness and prolong shelf life. Metabolome analysis confirmed the decline of lipids and the accumulation of organic acids in litchi fruits in response to 6PP treatment. These effects from 6PP could alleviate disease effects and prolong the shelf life of litchi fruits. These findings suggested that 6PP could be a useful natural product to control downy blight disease and a new preservative of litchi fruits.

A New Insight into 6-Pentyl-2H-pyran-2-one against Peronophythora litchii via TOR Pathway.

The litchi downy blight disease of litchi caused by Peronophythora litchii accounts for severe losses in the field and during storage. While ample quantitative studies have shown that 6-pentyl-2H-pyran-2-one (6PP) possesses antifungal activities against multiple plant pathogenic fungi, the regulatory mechanisms of 6PP-mediated inhibition of fungal pathogenesis and growth are still unknown. Here, we investigated the potential molecular targets of 6PP in the phytopathogenic oomycetes P. litchii through integrated deployment of RNA-sequencing, functional genetics, and biochemical techniques to investigate the regulatory effects of 6PP against P. litchii. Previously we demonstrated that 6PP exerted significant oomyticidal activities. Also, comparative transcriptomic evaluation of P. litchii strains treated with 6PP Revealed significant up-regulations in the expression profile of TOR pathway-related genes, including PlCytochrome C and the transcription factors PlYY1. We also noticed that 6PP treatment down-regulated putative negative regulatory genes of the TOR pathway, including PlSpm1 and PlrhoH12 in P. litchii. Protein-ligand binding analyses revealed stable affinities between PlYY1, PlCytochrome C, PlSpm1, PlrhoH12 proteins, and the 6PP ligand. Phenotypic characterization of PlYY1 targeted gene deletion strains generated in this study using CRISPR/Cas9 and homologous recombination strategies significantly reduced the vegetative growth, sporangium, encystment, zoospore release, and pathogenicity of P. litchii. These findings suggest that 6PP-mediated activation of PlYY1 expression positively regulates TOR-related responses and significantly influences vegetative growth and the virulence of P. litchii. The current investigations revealed novel targets for 6PP and underscored the potential of deploying 6PP in developing management strategies for controlling the litchi downy blight pathogen.

Comparative physiological and transcriptome analysis provide insights into the inhibitory effect of 6-pentyl-2H-pyran-2-one on Clarireedia jacksonii.

Clarireedia spp. is a destructive phytopathogenic fungus that causes turf dollar spot of bent-grass, leading to widespread lawn death. In this study, we explored the antifungal capability of 6-pentyl-2H-pyran-2-one (6PP), a natural metabolite volatilized by microorganisms, which plays an important role in the biological control of turfgrass dollar spot. However, the mechanisms by which 6PP inhibits Clarireedia jacksonii remain unknown. In the present study, C. jacksonii mycelial growth was inhibited by the 6PP treatment and the 6PP treatment damaged cell membrane integrity, causing an increase in relative conduc-tivity. Furthermore, physiological and biochemistry assay showed that 6PP treatment can enhance reactive oxygen species (ROS) levels, malondialdehyde (MDA) content obviously increased with 6PP exposure, increased alchohol dehydrogenase (ADH) and depleted acetalde-hyde dehydrogenase (ALDH), and activated the activities of many antioxidant enzymes in C. jacksonii. Gen Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that some genes in C. jacksonii after 6PP treatment related to integrity of the cell wall and membrane, and oxidative stress were significantly downregulated. It is worth mentioning that the fatty acid degradation pathway is significantly upregulated, with an increase in ATP content and ATP synthase activity, which may promote fungal cell apoptosis. Moreover, we found that the expression of ABC transporters, and glutathione metabolism encoding genes were increased to respond to external stimuli. Taken together, these findings revealed the potential antifungal mechanism of 6PP against Clarireedia spp., which also provides a theoretical basis for the commercial utilization of 6PP as a green pesticide in the future.

An overview of structure-based activity outcomes of pyran derivatives against Alzheimer's disease.

Pyran is a heterocyclic group containing oxygen that possesses a variety of pharmacological effects. Pyran is also one of the most prevalent structural subunits in natural products, such as xanthones, coumarins, flavonoids, benzopyrans, etc. Additionally demonstrating the neuroprotective properties of pyrans is the fact that this heterocycle has recently attracted the attention of scientists worldwide. Alzheimer's Disease (AD) treatment and diagnosis are two of the most critical research objectives worldwide. Increased amounts of extracellular senile plaques, intracellular neurofibrillary tangles, and a progressive shutdown of cholinergic basal forebrain neuron transmission are often related with cognitive impairment. This review highlights the various pyran scaffolds of natural and synthetic origin that are effective in the treatment of AD. For better understanding synthetic compounds are categorized as different types of pyran derivatives like chromene, flavone, xanthone, xanthene, etc. The discussion encompasses both the structure-activity correlations of these compounds as well as their activity against AD. Because of the intriguing actions that were uncovered by these pyran-based scaffolds, there is no question that they are at the forefront of the search for potential medication candidates that could treat Alzheimer's disease.

(23R,231 S,25S)-231,26-Ep-oxy-23-ethyl-furost-20(22)-en-3ß-ol.

The title compound, C29H46O3, is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring F is a tetra-hydro-2H-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while di-hydro-furan ring E, to which it is bonded, has an envelope conformation. The mol-ecules are associated by weak O-H⋯O hydrogen bonds to form chains running in the [101] direction in the crystal.

Design, synthesis and antitumor activity of novel pyran-functionalized uracil derivatives: docking studies.

Aim: Synthesis of novel pyran-based uracils that may have potent antitumor activity against hepatocellular carcinoma HepG2 and ovarian cancer SKOV3 cell lines. Materials & methods: Novel pyran-based uracils were synthesized and their anticancer activity was assessed using methyl thiazolyl tetrazolium and wound-healing assays to detect their cytotoxicity and their antiproliferative and antimigratory activities. Results: Compounds 3, 5, 6, 7, 8, 9, 10, 11 and 13 significantly inhibited cell proliferation of the HepG2 cell line. Compounds 7, 8, 9 and 13 significantly inhibited the proliferation of SKOV3 cells, which was also proven through docking studies with topoisomerase I. Conclusion: The molecular docking analysis revealed that 7 and 9 are two major compounds found to possess higher degrees of interaction with DNA gyrase.