Benzofuran Derivative Research Articles

Amiodarone Therapy: Updated Practical Insights.

Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation while also playing a crucial role in preventing a range of ventricular arrhythmias. Amiodarone has a complex pharmacokinetic profile, characterized by a large volume of distribution and a long half-life, which can range from several weeks to months, resulting in prolonged effects even after discontinuation. Side effects may include thyroid dysfunction, pulmonary fibrosis, and hepatic injury, necessitating regular follow-ups. Additionally, amiodarone interacts with several drugs, including anticoagulants, which must be managed to prevent adverse effects. Therefore, a deep understanding of both oral and intravenous formulations, as well as proper dosage adjustments, is essential. The aim of this paper is to provide a comprehensive and updated review on amiodarone's indications, contraindications, recommended dosages, drug interactions, side effects, and monitoring protocols.

An exploration into CTEPH medications: Combining natural language processing, embedding learning, in vitro models, and real-world evidence for drug repurposing.

In the modern era, the growth of scientific literature presents a daunting challenge for researchers to keep informed of advancements across multiple disciplines. We apply natural language processing (NLP) and embedding learning concepts to design PubDigest, a tool that combs PubMed literature, aiming to pinpoint potential drugs that could be repurposed. Using NLP, especially term associations through word embeddings, we explored unrecognized relationships between drugs and diseases. To illustrate the utility of PubDigest, we focused on chronic thromboembolic pulmonary hypertension (CTEPH), a rare disease with an overall limited number of scientific publications. Our literature analysis identified key clinical features linked to CTEPH by applying term frequency-inverse document frequency (TF-IDF) scoring, a technique measuring a term's significance in a text corpus. This allowed us to map related diseases. One standout was venous thrombosis (VT), which showed strong semantic links with CTEPH. Looking deeper, we discovered potential repurposing candidates for CTEPH through large-scale neural network-based contextualization of literature and predictive modeling on both the CTEPH and the VT literature corpora to find novel, yet unrecognized associations between the two diseases. Alongside the anti-thrombotic agent caplacizumab, benzofuran derivatives were an intriguing find. In particular, the benzofuran derivative amiodarone displayed potential anti-thrombotic properties in the literature. Our in vitro tests confirmed amiodarone's ability to reduce platelet aggregation significantly by 68% (p = 0.02). However, real-world clinical data indicated that CTEPH patients receiving amiodarone treatment faced a significant 15.9% higher mortality risk (p<0.001). While NLP offers an innovative approach to interpreting scientific literature, especially for drug repurposing, it is crucial to combine it with complementary methods like in vitro testing and real-world evidence. Our exploration with benzofuran derivatives and CTEPH underscores this point. Thus, blending NLP with hands-on experiments and real-world clinical data can pave the way for faster and safer drug repurposing approaches, especially for rare diseases like CTEPH.

Effect of Amiodarone on the Thyroid Gland of Adult Male Albino Rats: A Histological and Morphometric Study

Abstract Background Amiodarone (AMD) is a benzofuran derivative, used in management of angina and refractory ventricular arrhythmia. Amiodarone has been associated with toxicity on many organs involving the lungs, thyroid gland, liver, eyes, skin, and nerves. Aim of the Work The aim of the current work was to study the structural and functional changes of the thyroid gland of adult male albino rats after exposure to the antiarrhythmic drug “Amiodarone”. Material and Methods Thirty adult male albino rats were used and divided into three groups. The first group included 10 rats which served as (control); 5 rats received distilled water orally and 5 rats received 3 ml of 0.6% methylcellulose. The second group included 10 rats used as (therapeutic dose treated group), which received 30 mg/Kg B.W. of amiodarone for 12 weeks by oral gavage, while the third group included 10 rats used as a (toxic dose treated group) which received 60 mg/Kg b. w. of amiodarone daily for 6 weeks by oral gavage. Serum concentration of tri-iodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) were evaluated. Morphometric study and statistical analysis were done. Results Biochemical examination revealed statistical highly significant increase (P &amp;lt; 0.001) of serum (T4 &amp; T3) with concomitant statistical highly significant decrease of (TSH) (P &amp;lt; 0.001). Histopathological examination of the thyroid tissues from the therapeutic dose treated group showed marked evidence of thyrotoxicosis in the form of microcystic follicular changes and peripheral scalloping, cellular degeneration with scanty cytoplasm and vesicular nuclei. These changes became more severe in toxic dose treated group in the form of thyroid tissue damage with hemorrhage and necrosis. Epithelial hyperplasia with atypical nuclear features were also detected. Conclusion Amiodarone had detrimental effects on the adult male albino rat’s thyroid tissue when administered either in the therapeutic or the toxic doses.

Synthesis of Benzofuran-Fused Oxepines through Cs2CO3-Promoted [4 + 3] Annulation of Aurones with Crotonate-Derived Sulfonium Salts.

Benzofuran-fused derivatives display important and reliable therapeutic properties. Herein, we describe the synthesis of benzofuran-fused oxepines using aurones and crotonate-derived sulfonium salts via a [4 + 3] annulation reaction in the presence of Cs2CO3. This reaction proceeds under mild and operationally simple conditions. The synthetic utility of this approach was highlighted by several transformations, including the efficient synthesis of a novel tetracyclic fused benzofuran derivative.

Designing novel benzofuran derived AIE-probes: dual-mode fluorescence turn-off and naked-eye color change for hydrazine detection

We report the molecular engineering of a benzofuran derivative to construct aggregation induced emissive (AIE) luminogens for hydrazine detection through dual mode fluorescence turn-off and naked eye color change mechanisms.

P-283 - Evaluation of Pyridyl Benzofuran Derivative for Targeted Alpha Therapy of Alzheimer’s Disease

P-283 - Evaluation of Pyridyl Benzofuran Derivative for Targeted Alpha Therapy of Alzheimer’s Disease

Pharmacodynamic Mechanisms of the Development of Pulmonary Fibrosis Due to Amiodarone use

Introduction: Amiodarone is a benzofuran derivative with highly effective class III antidysrhythmic activity used in ventricular and supraventricular arrhythmia; however, its most side effect is pulmonary toxicity, with an incidence of 0 to 10%, and a mortality of 1 to 33%. The mechanism of the adverse reaction is still a matter of investigation. Therefore, the overall objective of this study is to determine the time in which pulmonary fibrosis develops from the use of amiodarone, which we hope to obtain with the following research question: What is the time in which pulmonary fibrosis develops from the use of amiodarone? Discussion: based on the sources reviewed, these establish that there is a risk of developing pulmonary adverse reactions from the therapeutic use of amiodarone directly related to the serum concentrations of the drug, but complete these data with broader populations. Conclusions: We were able to determine from the literature review that lung injury can be activated by low and high therapeutic doses of amiodarone.

Estimation of dipole moments by Solvatochromic shift method, spectroscopic analysis of UV–Visible, HOMO-LUMO, ESP map, Mulliken atomic charges, NBO and NLO properties of benzofuran derivative

Solvatochromic shift method has been used to estimate ground state (μg) and excited state (μe) dipole moments of benzofuran derivative (5NFMOT) at room temperature indifferent solvents. This method involves Lippert, Bakhshiev and Kawski-Chamma-Viallet equations. Reichardt microscopic solvent polarity parameter was used to calculate the change in dipole moment. Effect of solvents on absorption and fluorescence spectra was investigated using Kamlet and Catalan's MLR approach. Computational studies of benzofuran derivative were carried out using Gaussian 16. Geometry optimization was performed using DFT method at 6–311++G (d, p)/B3LYP basis set. UV–Visible spectra have been studied by using TD-DFT method for the same basis set. The μg was obtained from DFT method, whereas μe from TD-DFT method. It has been observed that both from experimentally and theoretically the ground state dipole moment is higher than the excited state dipole moment. HOMO-LUMO surfaces and Mulliken atomic charges have been studied in gas phase and solution. Furthermore, 3D plots of electrostatic potential map are used to identify reactive centers such as electrophilic and nucleophilic sites. NBO analysis is helpful to obtain stability and charge delocalization of the title molecule. Polarizablity, and hyper polarizability values were used to study the NLO properties.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects of BMBF in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7-an HCC cell line with a mutated p53 gene (Y220C). According to a scratching motility assay, non-cytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial-mesenchymal transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7, deactivated its downstream signal FAK/AKT, and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in the prevention of cell invasion because of the reduction in integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5-an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in downregulating p53 and mediating the suppression of integrin α7, EMT, and MMP-9 in HCC cells with a mutated p53 gene.

One undescribed glycoside benzofuran derivative and a new p-hydroxybenzoate glycoside from the leaves of Illicium dunnianum Tutcher

One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3–8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 μM), compounds 1–8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380–655 μM.

Garcinia oligantha: A comprehensive overview of ethnomedicine, phytochemistry and pharmacology.

Garcinia oligantha Merr. is an ethnomedicine plant mainly distributed in Guangdong and Hainan, China. It has the effects of heat-clearing and detoxicating, which has been used by local ethnic minorities to treat a variety of diseases, including inflammation, internal heat, toothache and scald. This review summarizes and discusses the progress of the chemical compounds and biological activities of G. oligantha that have been studied in recent years to provide the direction for the prospective research and applications of G. oligantha. The relevant literature about G. oligantha was accessible from ancient Chinese medical books and records, theses, as well as major scientific databases such as Google Scholar, PubMed, Web of Science, ScienceDirect, SciFinder, Baidu Scholar and China National Knowledge Infrastructure (CNKI). To date, more than 150 chemical compounds were isolated from this plant, including xanthones, volatile oil, fatty acid, benzofurane derivative and biphenyl compounds. Xanthones are the main bioactive compounds that exhibit diverse biological effects, such as antitumor, analgesic, anti-inflammatory, antioxidative, neuroprotective, antimalarial and antibacterial effects, which are consistent with its traditional uses as a folk medicine. Modern pharmacological studies show that these compounds participate in a variety of signaling pathways underlying different pathophysiologies, making them a valuable medicinal resource. G. oligantha is an ethnomedicine with a long history. However, due to regional and cultural constraints, the popularisation and use of ethnomedicine are still limited. Modern pharmacological and chemical research suggest that G. oligantha contains a variety of bioactive compounds and showed diverse biological functions, which is worthy of comprehensive and in-depth research. This review summarizes and discusses the recent progress in studies on G. oligantha, looking forward to promote further research and sustainable development of folk medicinal plants.

Dibetanide, a new benzofuran derivative with the rare conjugated triene side chain from a sponge-associated fungus Aspergillus species

Benzofuran-containing compounds are found to be promising scaffold with a wide range of pharmacological properties for drug development. A new benzofuran derivative, dibetanide (1), along with a known analogue, vermistatin (2), were discovered successfully from the culture extract of the sponge-associated fungus Aspergillus sp. LS57. Structurally, the new compound dibetanide featured the unusual conjugated triene side chain, which was isolated here for the first time in benzofuran derivatives. Their structures were deduced from HRESIMS, 1D and 2D NMR spectroscopy, and the absolute configurations were further determined by computational electronic circular dichroism (ECD) and comparison of experimental ECD spectra. Compounds 1 and 2 were evaluated for antifungal, antiviral and antibacterial activities, while only 1 exhibited inhibitory activity against Botrytis cinerea in vitro.

Anti-inflammatory compounds from the mangrove endophytic fungus Amorosia sp. SCSIO 41026.

Three new chlorinated compounds, including two propenylphenol derivatives, chlorophenol A and B (1 and 2), and one benzofuran derivative, chlorophenol C (3), together with 16 known compounds, were isolated from the mangrove endophytic fungus Amorosia sp. SCSIO 41026. 7-Chloro-3,4-dihydro-6,8-dihydroxy-3-methylisocoumarine (4) and 2,4-dichloro-3-hydroxy-5-methoxy-toluene (5) were obtained as new natural products. Their structures were elucidated by physicochemical properties and extensive spectroscopic analysis. Compounds 1, 4, 7, 9, 13, 15, 16, and 19 possessed inhibitory effects against the excessive production of nitric oxide (NO) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-challenged RAW264.7 macrophages without obvious cytotoxicity. Moreover, 5-chloro-6-hydroxymellein (13) further alleviated the pathological lung injury of LPS-administrated mice and protected RAW264.7 macrophages against LPS-induced inflammation through PI3K/AKT pathway in vivo. Our research laid the foundation for the application of compound 13 as a potential anti-inflammatory candidate.

Aromatic Polyketides from the Deep-Sea Cold-Seep Mussel Associated Endozoic Fungus Talaromyces minioluteus CS-138.

Five new aromatic polyketides, including a unique benzofuran derivative, talarominine A (1), and four chromone analogs talamins A–D (2–5), along with one known related metabolite, 5-hydroxy-7-methoxy-2,3-dimethylchromone (6), were isolated and identified from the Talaromyces minioluteus CS-138, an endozoic fungus obtained from the deep-sea cold seep mussel Gigantidas platifrons. Their chemical structures were elucidated by detailed analysis of their NMR spectra, HRESIMS and X-ray crystallographic data, and by comparison with literature data as well. The antibacterial and DPPH scavenging activities of compounds 1–6 were evaluated. Compounds 1–3 showed inhibitory activity against some of the tested bacteria whereas compounds 2 and 5 showed potent DPPH radical scavenging activities, which were better than that of the positive control butylated hydroxytoluene (BHT). This work is likely the first report on marine natural products of mussel-derived fungus living in cold seep environments.

124I]IBETA: A New Aβ Plaque Positron Emission Tomography Imaging Agent for Alzheimer's Disease.

Several fluorine-18-labeled PET β-amyloid (Aβ) plaque radiotracers for Alzheimer’s disease (AD) are in clinical use. However, no radioiodinated imaging agent for Aβ plaques has been successfully moved forward for either single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Radioiodinated pyridyl benzofuran derivatives for the SPECT imaging of Aβ plaques using iodine-123 and iodine-125 are being pursued. In this study, we assess the iodine-124 radioiodinated pyridyl benzofuran derivative 5-(5-[124I]iodobenzofuran-2-yl)-N,N-dimethylpyridin-2-amine ([124I]IBETA) (Ki = 2.36 nM) for utilization in PET imaging for Aβ plaques. We report our findings on the radioiododestannylation reaction used to prepare [124/125I]IBETA and evaluate its binding to Aβ plaques in a 5 × FAD mouse model and postmortem human AD brain. Both [125I]IBETA and [124I]IBETA are produced in >25% radiochemical yield and >85% radiochemical purity. The in vitro binding of [125I]IBETA and [124I]IBETA in transgenic 5 × FAD mouse model for Aβ plaques was high in the frontal cortex, anterior cingulate, thalamus, and hippocampus, which are regions of high Aβ accumulation, with very little binding in the cerebellum (ratio of brain regions to cerebellum was >5). The in vitro binding of [125I]IBETA and [124I]IBETA in postmortem human AD brains was higher in gray matter containing Aβ plaques compared to white matter (ratio of gray to white matter was >5). Anti-Aβ immunostaining strongly correlated with [124/125I]IBETA regional binding in both the 5 × FAD mouse and postmortem AD human brains. The binding of [124/125I]IBETA in 5 × FAD mouse and postmortem human AD brains was displaced by the known Aβ plaque imaging agent, Flotaza. Preliminary PET/CT studies of [124I]IBETA in the 5 × FAD mouse model suggested [124I]IBETA was relatively stable in vivo with a greater localization of [124I]IBETA in the brain regions with a high concentration of Aβ plaques. Some deiodination was observed at later time points. Therefore, [124I]IBETA may potentially be a useful PET radioligand for Aβ plaques in brain studies.

Cascade transformation of 4-hydroxymethyl-2-carene into novel cage methanopyrano[4,3-b]thieno[3,2-g]benzofuran derivative

Reaction of trans-4-hydroxymethyl-2-carene with thiophene- 2-carbaldehyde under heterogeneous catalysis by K10 clay affordsubstitutedmethanopyrano[4,3-b]thieno[3,2-g]- benzofuran, a complex 5-membered chiral cage heterocyclic compound containing two thiophene moieties. Its structure was determined by 1D and 2D NMR experiments (HSQC, HMBC, COSY, NOESY) and HRMS.

Three new compounds isolated from the whole plants of Salsola collina pall

One new alkaloid, 6, 7-dimethoxyisoquinoline-N-oxide (1), one new benzofuran derivative, 3,7-dimethyl-6-acetyl-8-benzofuranol (2) and one new lignan, salsolains A (3), along with seven known compounds (4–10), were isolated from the whole plant of Salsola collina Pall. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1 D and 2 D NMR), and their absolute configurations were determined by the X-ray crystallography and ECD calculation. The activities of compounds 1–10 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, especially, compound 5 (50 μM) exhibited the most significant anti-inflammatory activity with the secretion levels of IL-6 and TNF-α at 3.87% and 4.03%, respectively.

The Chinese expert recommendations on the clinical use of dronedarone

Dronedarone, a class Ⅲ antiarrhythmic drug, is a deiodinated benzofuran derivative of amiodarone. It has similar antiarrhythmic effects with amiodarone, but much lesser adverse effects than amiodarone, particularly in those outside the heart. It is suggested to use dronedarone for the rhythm control of atrial fibrillation/flutter, for it has been shown to prevent the recurrence of atrial fibrillation/flutter and reduce rehospitalization in patients with paroxysmal or persistent atrial fibrillation/flutter. Dronedarone is not recommended for the rhythm control in patients with long-term persistent atrial fibrillation or permanent atrial fibrillation, and atrial flutter or atrial fibrillation patients with reduced ejection fraction. Liver function, electrolyte tests and an electrocardiogram should be performed before and after the drug initiation. Potential interactions with other kinds of drugs have to be taken into consideration as well.

A new benzofuran compound from the resinous exudates of Commiphora myrrha

A new benzofuran derivative, identified as myrrhain A (1), was isolated from the resinous exudates of Commiphora myrrha, together with the four known compounds: commipharane (2), myrrhterpeniod (3), myrrhone (4), and 9-methoxymyrrhone (5). All structures were elucidated by NMR and MS analyses. DPPH assay of compounds 1–5 revealed for the first time that all of them possess moderate antioxidative activity.

Two new chemical constituents from the leaves of Illicium dunnianum

One new phenolic glycoside (1) and one new benzofuran derivative (2) were isolated from the leaves of Illicium dunnianum. The structures of these compounds were established by using comprehensive spectroscopic data analysis, including the 1D and 2D NMR, IR, HR-ESI-MS, electronic circular dichroism and comparison with literature data. All isolates were evaluated for the inhibition against the production of NO by LPS-stimulated RAW 264.7 macrophages.