Chromone Derivatives Research Articles

Structural Characterization and Hepatoprotective Activities of 2-(2-Phenylethyl)Chromone Derivatives from Highland Barley Monascus purpureus

Structural Characterization and Hepatoprotective Activities of 2-(2-Phenylethyl)Chromone Derivatives from Highland Barley Monascus purpureus

Analysis of the components of Cassia nomame and their antioxidant activity

Cassia nomame, an annual herb belonging to the Leguminosae family, is traditionally consumed as tea in the form of dried whole herbs or beans. To deepen our understanding of the chemical constituents of C. nomame, we isolated 16 compounds, categorised as flavone derivatives (1–4), including a novel compound nomameflavone A (4), a chalcone derivative (5), an aurone derivative (6), a chromone derivative (7), a juglone derivative (8), anthraquinone derivatives (9–11), phenolic compounds (12–14), and sterol derivatives (15, 16). The structure of each compound was elucidated using NMR and MS. Compounds 2, 6, 7, 8, 12, 13, and 14 were successfully isolated from C. nomame for the first time. Furthermore, compounds 1, 3, 5, and 6 exhibited DPPH radical scavenging activities, and the bioactivity of 3 was discovered. The elucidation of the diverse chemical constituents of C. nomame underscores its potential functional ingredients.

Chromone Derivatives as a Novel NOX4 Inhibitor: Design, Synthesis, and Regulation of ROS in Renal Fibroblast.

Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) has emerged as a promising target for developing drugs to tackle renal fibrosis. In this study, a series of chromone derivatives were designed and synthesized. Additionally, we established a NOX4 overexpression model using the NRK-49F rat renal fibroblasts cell line and identified compound 14m as highly active through the assessment of intracellular reactive oxygen species (ROS) levels in this model. The drug affinity responsive target stability (DARTS) assay illuminated the robust binding stability of 14m with NOX4. Mechanistic studies further substantiated its efficacy in ameliorating fibrosis and inflammation. This investigation positions 14m as a noteworthy NOX4 inhibitor, shedding light on its regulatory role in renal fibroblasts. Importantly, it diversifies the structural landscape of NOX4 inhibitors, offering novel lead compounds for future development.

Design, Synthesis and Molecular Docking Studies of Tailored Coumarin and Chromone Derivatives for Use as Anti-Alzheimer Agents

Design, Synthesis and Molecular Docking Studies of Tailored Coumarin and Chromone Derivatives for Use as Anti-Alzheimer Agents

A New Isoflavone Xylopyranoside and Isoflavone Derivatives from the Roots of Ochna integerrima and Their DPPH Radical Scavenging Activity.

O chna integerrima (Louri) Merr. is one of the two species of the genus Ochna (family Ochnaceae) found in Thailand. Its bark is used in traditional Thai medicine to treat digestive disorders. Phytochemical investigation of the crude MeOH extract of the root woods of O. integerrima furnished an unreported isoflavone glycoside, gerontoisoflavone A-4'-O-β-D-xylopyranoside (1), together with the previously described irisolone methyl ether (2), iriskumaonin methyl ether (3), iriskumaonin (4), gerontoisoflavone A (5), isoprunetin (6), a flavone glycoside, vitexin (7), and a chromone derivative, lophilone A (8). The structure of 1 was elucidated by 1D and 2D NMR spectral analysis as well as HRMS data. Compounds 1-7 were evaluated for their 2,2-diphenyl-1-picrylhydrazil radical(DPPH●) scavenging activity and antiplasmodial activity against a chloroquine- and pyrimethamine-resistant strain of Plasmodium falciparum (K1). Compounds 5 exhibited strongest scavenging activity, with a scavenging concentration at 50% (SC50) of 137.7 mM, while 4 and 6 displayed weak scavenging activity, with SC50 values of 4 and 5 times higher than that of 5. None of the tested compounds showed antiplasmodial activity against P. falciparum (K1) at a concentration of 5 mg/mL.

Total Synthesis of Chalaniline A: An Aminofulvene Fused Chromone from Vorinostat-Treated Fungus Chalara sp. 6661.

Chalaniline A, an aminofulveno[1,2-b]chromone derivative previously isolated from a vorinostat-treated ascomycete Chalara sp., was prepared in nine steps from orcinol (3,5-dihydroxytoluene). In a key transformation, the tricyclic ring system of the target was generated by a pyrrolidine-catalyzed double annulation between α-(methylsulfinyl)-2,6-dihydroxy-4-methylacetophenone and the ketaldoester, methyl 2,5-dioxopentanoate. The resulting tertiary alcohol (coniochaetone H) was further converted to chalaniline A by operations including dehydration (to yield a hydroxyfulvene), Vilsmeier reaction, and enamine exchange.

In vivo efficacy of date palm pit extract based chromone derivative against Aedes aegypti dengue vectors in Saudi Arabia

AbstractThis study investigated the in vivo efficacy of a chromium derivative extracted from date palms pit against Aedes aegypti the third instar larvae, the known vector of dengue fever in Saudi Arabia. Chromone 1, a flavonoid chromone component, was isolated from the alcoholic extract of date palm pits (DPP) using High‐performance liquid chromatography (HPLC). The results showed that exposure of A. aegypti larvae to whole DPP extract and chromone 1 for 24 h resulted in significant insecticidal efficacy with LC50 values of 132.82 and 54.64 ppm, respectively. The same concentrations also effectively inhibited AChE (acetylcholinesterase) activity up to −56.83 and −58.58%, respectively, compared to controls. The acetylcholine bromide test further confirmed the interaction between chromone 1 and AChE. The results also revealed that the chromone 1 treatment altered Deoxyribonucleic Acid (DNA) and protein content. It also exhibited that the extract of date palm pits DPP can effectively serve as sustainable ingredients for the control management of A. aegypti.

Green synthesis and biological significance of chromone derivatives with amino acid and their metal complexes as antimicrobial, anti-diabetic and anti-oxidant

A new organic compound designed by reaction of 3-formyl-6-methylchromone with alanine amino acid and its metal chelates of Ni(II), Fe(II), Co(II), Zn(II) and Zr(IV) ions were synthesized by employing two approaches i.e. green method (microwave irradiation)and conventional method that further compared with each other. All compounds were characterized with various physical analysi (melting point determination, elemental analysis, molar conductance measurement, magnetic moment determination), chemical analysis and various spectral techniques i.e., UV–Vis, FTIR, 1H NMR, Mass spectra and evaluated for in vitro antimicrobial (antifungal: C. albicans, T. reesei; antibacterial: B. subtilis, S. aureus, E. coli), anti-diabetic and anti-oxidant activities. Synthesized compounds were investigated for their thermal stability and crystallinity through thermogravimetric analysis and powder-XRD technique. All analytical data suggested that the 3d series transition metal complexes have tetrahedral geometry and Zr(IV) complex has octahedral geometry. Fe(II) complex exhibited good to moderate both antibacterial and antifungal activity against all selected pathogens. Other metal complexes has shown almost similar antimicrobial potential as ligand. Among all synthesized compounds Ni(II) complex displayed highest anti-diabetic (IC50 = 61.71 mg/L) and anti-oxidant activity (IC50 = 592.38 mg/L). Other metal chelates are less effective for anti-diabetic and anti-oxidant activity compared to ligand.

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1–16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO–LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of − 8.5 kcal mol−1. This result outperformed the affinity of the reference standard dapagliflozin (− 7.9 kcal mol−1) as well as two other compounds that target human IDE, namely vitexin (− 8.3 kcal mol−1) and myricetin (− 8.4 kcal mol−1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein–ligand complex at the active site.

Divergent synthesis of chromones and chromanones from diketones using an AgOTf/[Si]H system by switching hydrosilanes

A method of using AgOTf/[Si]H for the efficient and divergent synthesis of chromones and chromanones from a common substrate via reductive coupling cyclization by switching hydrosilanes has been developed. Results of mechanistic studies revealed that under Ph2MeSiH conditions, the reaction initially undergone cyclization to form chromones 2a, which can subsequently be reduced to yield chromanones 3a. When the hydrosilane was switched to Et3SiH, the reaction route stopped at chromone 2a and C2C3 could not be further reduced. This novel, mild protocol features broad functional group compatibility, high product diversity, and utility in constructing biorelevant chromone or chromanone derivatives.

Chromones and biflavonoids from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity

Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones, garpedunchromones A-C (1–3), and one biflavonoid, nujiangbiflavone A (14), along with fifteen known analogs (4–13, 15–19) were isolated from G. pedunculata and G. nujiangensis. The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B (2) was the most active with an IC50 value of 18.11 ± 0.96 μM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.

Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (-102.589 kJ/mol). MIC and CFM values ranged from 264.52 μM (62.5 μg/mL) to 4232.44 μM (1000 μg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.

In Vitro and In Vivo Investigations of Chromone Derivatives as Potential Multitarget-Directed Ligands: Cognitive Amelioration Utilizing a Scopolamine-Induced Zebrafish Model.

Alzheimer's disease is a complex neurological disorder linked with multiple pathological hallmarks. The interrelation of therapeutic targets assists in the enhancement of cognitive decline through interference with overall neuronal transmission. We have synthesized and screened various chromone derivatives as potential multitarget-directed ligands for the effective treatment of Alzheimer's disease. The synthesized compounds exhibited multipotent activity against AChE, BuChE, MAO-B, and amyloid β aggregation. Three potent compounds, i.e., VN-3, VN-14, and VN-19 were identified that displayed remarkable activities against different targets. These compounds displayed IC50 values of 80 nM, 2.52 μM, and 140 nM against the AChE enzyme, respectively, and IC50 values of 2.07 μM, 70 nM, and 450 nM against the MAO-B isoform, respectively. VN-3 displayed potent activity against self-induced Aβ1-42 aggregation with inhibition of 58.3%. In the ROS inhibition studies, the most potent compounds reduced the intracellular ROS levels up to 80% in SH-SY5Y cells at 25 μM concentration. The compounds were found to be neuroprotective and noncytotoxic even at a concentration of 25 μM against SH-SY5Y cells. In silico studies showed that the compounds were nicely accommodated in the active sites of the receptors along with thermodynamically stable orientations. Compound VN-19 exhibited a balanced multitargeting profile against AChE, BuChE, MAO-B, and Aβ1-42 enzymes and was further evaluated for in vivo activities on the scopolamine-induced zebrafish model. VN-19 was found to ameliorate the cognitive decline in zebrafish brains by protecting them against scopolamine-induced neurodegeneration. Thus, VN-3, VN-14, and VN-19 were identified as potent multitarget-directed ligands with a balanced activity profile against different targets and can be developed as therapeutics for AD.

Synthesis, molecular docking studies and biological evaluation of N-(4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl) benzamides as potential antioxidant, and anticancer agents

A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K2CO3 and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR, 1H, and 13C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC50 values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities.

Bi-2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria filaria in the Philippines

Twelve undescribed 2-(2-phenethyl)chromone dimers (1−12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9−12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 μM.

Visible-Light-Triggered Difluoroacetylation/Cyclization of Chromone-Tethered Alkenes Enabling Synthesis of Tetrahydroxanthones.

Hydroxanthones have attracted considerable attention due to their significance in organic and biological chemistry, yet their synthesis remains a great challenge. In this study, a series of chromone-tethered alkenes are designed, and a radical cyclization reaction of these chromone derivatives has been achieved under photoredox conditions. The reaction uses bromodifluoroacetamides or bromodifluoroacetates as coupling partners, affording a broad range of functionalized tetrahydroxanthone products with up to 85% yields. The reaction is triggered via the generation of difluoroacetate radicals or alkene radical cations with fac-Ir(ppy)3 or 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene as a photocatalyst. This approach offers access to various tetrahydroxanthone derivatives from readily available starting materials and enriches the research content of heteroarene-tethered alkenes.

Chaetoxylariones A–G: undescribed chromone-derived polyketides from co-culture of Chaetomium virescens and Xylaria grammica enabled via the molecular networking strategy

By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A–G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8–12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7′ and C-10′; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 μM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.

Anti-inflammatory Polyketides from an Endophytic Fungus Chaetomium sp. UJN-EF006 of Vaccinium bracteatum.

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.

Anemhupehins D[sbnd]F, sterols and chromone derivative from Anemone hupehensis and their anti-inflammatory activity

Two previously undescribed plant sterols, namely anemhupehins D (1) and E (2), and one undescribed chromone derivative, namely anemhupehin F (3), have been isolated from the aerial parts of Anemone hupehensis. Their structures were elucidated by extensive spectroscopic data analyses and computational methods. All compounds were investigated for their anti-inflammatory and antibacterial activities. Compounds 1 and 2 showed inhibitory activity against NO production with IC50 values of 4.4 and 16.2 μM, respectively. All compounds had no antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa at the concentration of 128 μg/mL.

Two unprecedented neuroprotective 2-(2-phenylethyl)chromone derivatives from cultivated “Qi-Nan” agarwood of Aquilaria sinensis

Two unprecedented 2-(2-phenylethyl)chromone derivatives, (R)-2-[2-hydroxy-2-(3-hydroxy-4-methoxyphenyl)ethyl]chromone (1) and (R)-1-hydroxy-5-(4-hydroxyphenyl)-1-phenylpentane-3-one (2), with one known compound were isolated from cultivated “Qi-Nan” agarwood of Aquilaria sinensis. Their structures were elucidated by analysis of 1D and 2D NMR as well as HRESIMS. TDDFT-ECD calculation was used to determine the absolute configuration. At 50 μM, compounds 1 and 3 exhibited significant neuroprotective effect, enhancing the cell vitality of human neuroblastoma SH-SY5Y cells induced by H2O2 to 73.24 ± 0.43% and 74.71 ± 5.24%, respectively.