Chromone Derivatives Research Articles

A new chromone derivative from an endophytic Aspergillus sp. GXNU-B1

A new chromone derivative, aspergione A (1), along with seven known metabolites, was isolated from a mangrove endophytic fungus, Aspergillus sp. GXNU-B1, which was collected from mangrove Acanthus ilicifolius L. Their structures and the absolute configuration of 1 were elucidated based on the analysis of HR-ESI-MS, NMR, and ECD calculation. Compounds 1-8 were evaluated for their anti-inflammatory effects on the production of nitricoxide (NO). Compounds 1 and 8 have potent inhibitory effects against NO production in activated macrophages with IC50 values of 38.26 and 44.30 μM, respectively.

Progress of Metal-Based Anticancer Chemotherapeutic Agents in Last two Decades and their Comprehensive Biological (DNA/RNA Binding, Cleavage and Cytotoxicity Activity) Studies.

During last two decades, there has been an enormous growth in the discovery of innovative active inorganic anticancer complexes (exerting remarkable cytotoxicity at sub micro-molar levels) derived from myriad ligand scaffolds, mainly acting on cancerous vs healthy cells by either halting or inhibiting their uncontrolled growth. The phenomenal success of cisplatin to treat numerous forms of solid malignancies has placed metal-based drugs to the forefront of treatment strategies against cancers. More than 10,000 platinum anticancer complexes have been developed during the past 40 years, but only five drugs have been approved for usage in humans while ten more complexes are currently undergoing clinical trials. Most of the compounds have failed either at R&D stages or in preclinical trails. This has led to extensive investigations by researchers of medicinal chemistry, including our group to design and prepare tailored 3d-metallo-drugs and organotin(IV) compounds from some naturally occurring bioactive compounds, such as amino-acids, peptides, chromone derivatives and NSAID's etc. that were used either alone or in cocktail combination, capable of specifically targeting DNA, lnc RNAs and proteins. Furthermore, 3d-metal ions such as copper, cobalt and zinc etc. incorporated in these ligand framework are biocompatible and induce a unique multi-modal mechanism of cytotoxic action involving angiogenesis, ROS-induced DNA damage, apoptosis by p53 mitochondrial genes and caspases etc. The results observed a positive correlation between the binding affinity of complexes with DNA (as quantified by intrinsic binding constant values) and their cytotoxic behavior. Complexes with high DNA binding propensity were typically lethal against a diverse panel of malignant cell types compared to normal cells.

Synthesis of novel 6-substituted-3-formyl chromone derivatives as anti-leishmanial agents and their possible mechanism of action in Leishmania donovani

Eleven new compounds, including the hydrazones 4a-h, pyrazole 5, and pyrazole-oximes 7b-c, were synthesized by condensation reaction between 6-substituted (-H, -Me, -F) 3-formylchromones 1a-c with N-substituted hydrazines 2a-d and hydroxylamine hydrochloride 3. The synthesized compounds were evaluated for their in vitro antileishmanial activity to determine the IC50 values. Compounds 4b, 4c and 4e exhibited the strongest antileishmanial activity with IC50 values between 1.6 – 4.7 µm. A plausible mechanism of action is proposed for the antileishmanial activity of the above-mentioned compounds. We also studied the effect of these three compounds on macrophages, which represent the mammalian host-cell. The results obtained on this system were about one order of magnitude larger when compared to those of L. donovani, thus supporting these compounds potential as precursors of antileishmanial drugs.

Field and atom-based 3D-QSAR models of chromone (1-benzopyran-4-one) derivatives as MAO inhibitors

Monoamine oxidases (MAOs) are flavo-enzymes that aid in the oxidative deamination of neurotransmitters like dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that work by preventing the breakdown of brain neurotransmitters and regulating mood. MAO inhibitors that use the chromone (1-benzopyran-4-one) structure have been found to be quite effective in studies. The current study involves the creation of pharmacophore models, 3-D QSAR, virtual screening, and docking investigations, all of which are evaluated using various criteria. The investigation included 39 ligands that emerged pharmacophore AHRRR_1, as the best pharmacophore model with a survival score of 5.6485. The 3D QSAR investigation revealed a significant model with the values of R 2 = 0.9064 and Q 2 = 0.8239. Docking study revealed that compound 18 had the highest docking (−10.402 kcal/mol) score in the series and showed interactions with the essential amino acid TYR398 required for MAO inhibitory activity. ZINC compounds were screened using the created pharmacophore model, which was followed up with a virtual screening study. The ZINC compounds with the best XP docking scores are ZINC03113255, ZINC07777127, ZINC05166353 and ZINC09341502 (with docking scores −10.021, −9.486, −8.031 and −7.792 kcal/mol, respectively). ZINC03113255, which showed the best score, has binding interactions with amino acid residues, TYR326, TYR398 and LYS296 of monoamine oxidase B. The ADME analysis demonstrated the compound’s drug-like characteristics. The findings of this study may be used in the development of chromone compounds that target the MAO inhibitor. Communicated by Ramaswamy H. Sarma

Design and Synthesis of Chalcone and Chromone Derivatives as Antimicrobial Agents

Design and Synthesis of Chalcone and Chromone Derivatives as Antimicrobial Agents

I2-DMSO mediated dual α,β-C(sp2)–H functionalization/bicyclization of o-hydroxyphenyl enaminones to construct C2,C3-disubstituted chromone derivatives: chromeno[2,3-b]pyrrol-4(1H)-ones

An unprecedented dual α,β-C(sp2)–H functionalization/bicyclization strategy of o-hydroxyphenyl enaminones for the preparation of chromeno[2,3-b]pyrrol-4(1H)-ones has been established.

Seven new 2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria walla

Two rare flavonoid-2-(2-phenylethyl)chromones and five new dimeric 2-(2-phenylethyl)chromones were isolated from ethanol extract of agarwood of Aquilaria walla by LC-MS-guided fractionation procedure. Their structures were established based on extensive spectroscopic methods including HRESIMS, 1D and 2D NMR, as well as by comparison with the literature. Compound 1 showed cytotoxic activity against five human cancer cell lines with IC50 values ranging from 13.40 to 28.96 μM with cisplatin as the positive control.

Elicitation of Secondary Metabolites in Aquilaria malaccensis Lam. Callus Culture by Crude Mycelial Extract of Fusarium solani and Methyl Jasmonate

Agarwood is a resinous wood of great economic value produced by trees from the Thymelaeaceae family in response to stress. The natural formation of agarwood can take decades after exposure to the stressors. Artificial agarwood induction by inoculating the stem with fungi has been successfully demonstrated, but resin accumulation occurs very slowly. Cell suspension and callus cultures may serve as an alternative solution to provide a fast-growing plant material to produce artificial agarwood in a short period. Here, we induced agarwood formation in callus cultures of Aquilaria malaccensis by application of crude mycelial extracts of Fusarium solani strains GSL1 or GSL2, or methyl jasmonate (MeJA). After 20 days of treatment with elicitors, all treated calluses had less dry weight than the control group. The gas chromatography–mass spectrometry analysis identified 33 different secondary metabolites among all samples, four of which were present in all treatments and control, i.e., 1-docosene and 1-octadecene (alkenes), 4-di-tert-buthylphenol (phenolic), and benzenepropanoic acid (fatty acid). The 6-methoxy-2-(4-methoxyphenethyl)-4H-chromene-4-one, a chromone derivative, was only detected in callus elicited with the F. solani strain GSL2 and MeJA. All treated calli produced more fatty acid derivatives than the control group. We conclude that elicitors used in this study can induce the production of agarwood-related chemicals such as chromone and fatty acid in callus culture.

An integrated approach utilizing raman spectroscopy and chemometrics for authentication and detection of adulteration of agarwood essential oils.

Agarwood is a precious aromatic plant which has good pharmacological effects such as antidepressant and sedation. It also has good ornamental and collection value. However, due to it is long and complex production process, the output of agarwood essential oils (AEOs) is scarce, so the price is expensive, the quality is uneven, and the adulteration events is endless. From the commercial and pharmaceutical point of view, the authenticity and quality of the commercial products labeled as AEOs is very important. This paper tested the applicability of Raman spectroscopy combined with chemometrics in classification and authenticity identification of AEOs. In this study, Raman spectroscopy and principal component analysis (PCA) combined with partial least square discriminant analysis (PLS-DA) were used to comprehensively evaluate AEOs from different geographical origins and/or extracted by different methods which showed different characteristic bands. The characteristic component of AEOs, chromone derivatives, and two commonly used adulterants were also detected. These characteristic bands provide spectrum information of AEO samples and reference materials, which can be used as Raman spectral markers for the qualitative identification of AEOs. This study can provide a novel, fast and convenient method for identification of AEOs.

Four new chromone derivatives from the Arctic fungus Phoma muscivora CPCC 401424 and their antiviral activities.

The crude extract of the Arctic fungus Phoma muscivora CPCC 401424 displayed anti-influenza A virus activities which led us to investigated their secondary metabolites. Four new chromone derivatives, phomarcticones A-D (1-4) and five known chromone analogs (5-9) have been isolated from Arctic fungus Phoma muscivora CPCC 401424. Compounds 3 and 4 possess rare sulfoxide groups in chromone derivatives. Their structures and absolute configurations were elucidated by extensive analysis of spectroscopic data, electronic circular dichroism, and comparison with reported data. Compounds 3, 7, and 9 showed significant anti-influenza A virus activities with the IC50 values of 24.4, 4.2, and 2.7 μM, respectively.

Iodine Promoted Synthesis of S‐Benzoazolyl Chromones by a Three‐Component One‐Pot Reaction

AbstractIn the presence of iodine, the synthesis of S‐benzoazolyl chromone derivatives by one‐pot manner is reported. Thus, 2‐aminophenol firstly reacted with tetramethylthiuram disulfide (TMTD) to form 2‐mercaptobenzoxazole, and then coupled with 2‐hydroxyphenyl enaminones to obtain S‐benzoazolyl chromones through one‐pot manner. This method features mild conditions, easy operation, environmentally friendliness and wide substrate scopes, illustrating practical application value in organic synthesis.

A DFT/TDDFT Investigation on Fluorescence and Electronic Properties of Chromone Derivatives.

The development of quick and precise detection technologies for active compounds in vivo is critical for disease prevention, diagnosis and pathological investigation. The fluorescence signal of the fluorophore usually defines the probe's sensitivity to the chemical being examined. Many natural compounds containing flavone and isoflavone scaffolds exhibit a certain amount fluorescence, albeit with poor fluorescence quantum yields. Therefore, we used density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations to investigate the fluorescence characteristics of chromium-derived fluorophores in more depth. Different substituents are introduced at different positions of the chromone. As weak electron donor groups, alkyl and aromatic groups were discovered to have varying quantum yields on the fluorophore scaffold, and longer alkyl chains are favorable to enhance fluorescence quantum yield. In comparison to the amino group, substituted amino group can avoid group rotation, and the introduction of cyclic amines such as pyrrolidine and heterocyclic amines can improve optical characteristics. The electron-donating methoxy group at position 6 helps to increase the fluorescence quantum yield.

Synthesis, biological evaluation and molecular docking studies of chromone derivatives as potential α-glucosidase inhibitors

A series of chromone derivatives were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity by using in vitro methods and molecular docking studies. Some new synthetic compounds showed excellent α-glucosidase inhibitory activity with IC50 values in the range from 10.9 ± 0.29 to 146.50 ± 0.49 µM. Among them, compound 6m exhibited the most potent α-glucosidase inhibitory activity with an IC50 value of 10.9 ± 0.29 μM. Enzyme kinetic study demonstrated that 6m was a mixed-type inhibitor (Ki = 16.87 μM). Circular dichroism spectra and fluorescence quenching experiments further confirmed that the secondary structure of α-glucosidase was changed by the binding of 6m. Molecular docking studies showed that the aryl groups of 6m interactions with the residues Tyr-71, Phe-157, Phe-177, and Phe-300 formed the CH-π. Cell viability assay has shown that 6m exhibited low cytotoxic activity against human normal cell lines.

A Pair of Chromone Epimers and an Acetophenone Glucoside from the Mangrove Endophytic Fungus Mycosphaerella sp. L3A1.

Three new compounds, including a pair of chromone derivatives (1-2), and an acetophenone glucoside (3), together with three known compounds (4-6), were isolated from the mangrove endophytic fungus Mycosphaerella sp. L3A1. Their structures were elucidated by HR-ESI-MS analysis and extensive spectroscopic data. The absolute configurations of new compounds were determined using single-crystal X-ray diffraction analysis, electronic circular dichroism (ECD) calculations and chemical hydrolysis. In bioassays, compound 4 showed moderate cytotoxic activity against MDA-MB-435, HCT116, and SNB19 with IC50 values in the range of 18.5-26.29 μM.

New Polyketides from a Hydrothermal Vent Sediment Fungus Trichoderma sp. JWM29-10-1 and Their Antimicrobial Effects.

Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (1, 2, and 6-8) and seven known compounds (3-5 and 9-12) were obtained from the culture of the marine-derived fungus Trichoderma sp. JWM29-10-1. Their structures were identified by extensive spectrographic data analyses, including 1D and 2D NMR, UV, IR, and HR-ESI-MS. Further, the absolute configurations of new compounds were determined by circular dichroism (CD) spectrum and alkali-hydrolysis in combination with the in situ dimolybdenum CD method. Subsequently, the antimicrobial effects of these isolated compounds were assessed by examining the minimal inhibition concentration (MIC) with the broth microdilution assay. Compounds 1 and 2 exhibited potent antimicrobial activity against Helicobacter pylori, including multidrug-resistant strains, with MIC range values of 2-8 µg/mL. Moreover, compound 1 showed significant inhibitory effects on the growth of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and vancomycin-resistant Enterococcus faecium, which greatly threaten human health. This study demonstrates that chromone derivatives 1-2, especially for 1, could be potential lead compounds for the development of new antimicrobial agents and provides insight for future medicinal chemistry research.

Two new chromone derivatives from the rhizosphere soil fungus Ilyonectria robusta

Two new chromone derivatives (1 and 2), and two known compounds (3 and 4) were isolated from the rhizosphere soil fungus Ilyonectria robusta. Their planar structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Additionally, all the isolated compounds were evaluated for their antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli, but no obvious activity was observed at a concentration of 128 μg/mL.

Chemical constituents of Rumex dentatus L. and their antimicrobial and anti-inflammatory activities

Antimicrobial bioactivity-guided isolation of the root extract of Rumex dentatus L. resulted in the characterization of nineteen natural products, including three undescribed compounds (rumexs A−C). Rumexs A and B are rare anthraquinone-anthrone dimers consisting of an emodin-10-C-glycoside linked via C-10 to C-7 of a chrysophanol moiety. They differed only in their configuration at C-10; their absolute configurations were determined by NOESY and ECD analysis. LC-HRMS analysis was performed to identify nineteen compounds. Anthraquinone derivatives such as anthraquinone aglycone, oxanthrone C-glycoside, anthraquinone O-glycoside and anthraquinone dimer were found to be the dominant components of R. dentatus. In addition, naphthol, naphthoquinone, chromone, flavonoid, isocoumarin, and lignanamide derivatives were also identified. Chrysophanol and emodin were the most abundant compounds in the crude ethanol extract; their contents were determined by HPLC to be 7.38 and 5.74 mg/g, respectively. The fractions and isolated compounds were tested for their inhibitory activity against Staphylococcus aureus, Candida albicans, and Escherichia coli. Most of them showed inhibitory activity against S. aureus, some fractions and 2-methoxy-6-acetyl-7-methyljuglone exhibited moderate inhibitory activity against C. albicans, and 2-methoxy-6-acetyl-7-methyljuglone had moderate inhibitory effects against E. coli. Emodin exhibited inhibitory activity against NO release in LPS-reduced RAW264.7 cells in a concentration-dependent manner.

Chemical and Bioactivity Diversity of 2-(2-Phenylethyl)chromones in Agarwood: A Review.

2-(2-Phenylethyl)chromone derivatives are regarded as key components in agarwood. An oxygen-containing heterocycle with a benzoannelated γ-pyrone moiety form the bioactive core of 2-(2-phenylethyl)chromones. With different substituents and positions, 2-(2-phenylethyl)chromone derivatives exhibit diverse biological properties, such as antioxidant, antimicrobial, neuroprotective, anti-inflammatory, and acetylcholinesterase inhibitory activities. In this review, we summarized the studies (from January 1976 to September 2021) on phytochemistry, bioactivity and quality control of 2-(2-phenylethyl)chromones. These studies aimed to clarify the chemical specificity, diversity and structure-activity relationship of 2-(2-phenylethyl)chromones. In addition, we assumed that diverse factors such as tree species, induction methods and formation time contribute to the chemical diversity of 2-(2-phenylethyl)chromones. Furthermore, this review contends that different types of 2-(2-phenylethyl)chromones should be utilized in the quality control methods of agarwood.

Three New Chromone Derivatives from the Deep-Sea-Derived Fungus Penicillium thomii

Three New Chromone Derivatives from the Deep-Sea-Derived Fungus Penicillium thomii

Selenation of 2‐Hydroxyphenyl Enaminones with Se Powder to Generate ArSe‐subsituted Chromone Derivatives

AbstractA simple and efficient selenylation/cyclization of 2‐hydroxyphenyl enaminones towards the synthesis of ArSe‐subsituted chromone derivatives has been realized. This reaction is performed with selenium powder and aromatic iodides together in one‐pot under simple conditions, good yields of target products were obtained. Furthermore, the reaction can be also extended to sulfenylation/cyclization of 2‐hydroxyphenyl enaminones via using sulfur powder, demonstrating its wide application scope.