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Journal of Enzyme Inhibition and... Dec 2023Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with...
Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) () that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC (PARP1) = 74 nM, IC (PARP2) = 109 nM) and tubulin (IC = 1.4 µM)]. Further investigations confirmed the ability of to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.
Topics: Humans; Female; Tubulin Modulators; Tubulin; Poly(ADP-ribose) Polymerase Inhibitors; Cell Line, Tumor; Drug Screening Assays, Antitumor; Antineoplastic Agents; Apoptosis; Endometrial Neoplasms; Flavones; Benzopyrans; Cell Proliferation
PubMed: 37919954
DOI: 10.1080/14756366.2023.2276665 -
Molecules (Basel, Switzerland) Feb 2017Demethylisoencecalin () and caleins A () and C () (3.16-31.6 mg/kg, p.o.), the major components from an infusion of controlled postprandial glucose levels during an...
Demethylisoencecalin () and caleins A () and C () (3.16-31.6 mg/kg, p.o.), the major components from an infusion of controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of , , and , four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2-chromene (), herniarin (), scoparone (), and 4',7-dimethylapigenin (). In addition, the structure of calein C () was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6-316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2-chromene () was developed and validated according to standard protocols.
Topics: Animals; Asteraceae; Benzopyrans; Blood Glucose; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Hyperglycemia; Hypoglycemic Agents; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Oils, Volatile; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Sesquiterpenes; Solid Phase Microextraction; Toxicity Tests, Acute
PubMed: 28216594
DOI: 10.3390/molecules22020289 -
Molecules (Basel, Switzerland) Apr 2014(‒)-Encecanescin (1) has been isolated from the leaves of Eupatorium aschembornianum. Two conformers are present in the crystal structure as a result of molecular...
(‒)-Encecanescin (1) has been isolated from the leaves of Eupatorium aschembornianum. Two conformers are present in the crystal structure as a result of molecular disorder. The structure of 1 was established by 1H- and 13C-NMR spectroscopy in CDCl3 solution using 2D NMR techniques (gHSQC, gHMBC and NOESY). A Monte Carlo random search using molecular mechanics followed by the geometry optimization of each minimum energy structure using density functional theory (DFT) calculations at the B3LYP/6-31G* level and a Boltzmann analysis of the total energies generated accurate molecular models describing the conformational behavior of 1. The three most stable conformers 2-4 of compound 1 were reoptimized at the B3LYP/6-311++G(d,p) level of theory using CHCl3 as a solvent. Correlations between the experimental 1H- and 13C-NMR chemical shifts (δexp) have been found, and the GIAO/B3LYP/6-311++G(d,p) calculated magnetic isotropic shielding tensors (σcalc) for conformers 2 and 3, δexp=a+b σcalc, are reported. A good linear relationship between the experimental and calculated NMR data has been obtained for protons and carbon atoms.
Topics: Benzopyrans; Carbon; Chloroform; Crystallography, X-Ray; Eupatorium; Models, Molecular; Molecular Conformation; Monte Carlo Method; Plant Extracts; Plant Leaves; Protons; Quantum Theory; Solvents; Stereoisomerism; Thermodynamics
PubMed: 24739931
DOI: 10.3390/molecules19044695 -
Journal of Enzyme Inhibition and... Dec 2023Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high...
Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high pharmacological potential of the chromene scaffold as selective ligand of the IX and XII isoforms, two libraries of compounds, namely 2H-chromene and 7H-furo-chromene derivatives, with diverse substitution patterns were designed and synthesised. The structure of the newly synthesised compounds was characterised and their inhibitory potency and selectivity towards human CA off target isoforms I, II and cancer-associated CA isoforms IX and XII were evaluated. Most of the compounds inhibit CA isoforms IX and XII with no activity against the I and II isozymes. Thus, while the potency was influenced by the substitution pattern along the chromene scaffold, the selectivity was conserved along the series, confirming the high potential of both 2H-chromene and 7H-furo-chromene scaffolds for the design of isozyme selective inhibitors.
Topics: Humans; Carbonic Anhydrase IX; Carbonic Anhydrases; Carbonic Anhydrase I; Carbonic Anhydrase II; Structure-Activity Relationship; Carbonic Anhydrase Inhibitors; Neoplasms; Antigens, Neoplasm; Benzopyrans; Isoenzymes; Molecular Structure
PubMed: 37870190
DOI: 10.1080/14756366.2023.2270183 -
Vascular Health and Risk Management 2007Nebivolol is a highly selective beta1-adrenergic blocker that also enhances nitric oxide bioavailability via the L-arginine-nitric oxide pathway, leading to vasodilation... (Review)
Review
Nebivolol is a highly selective beta1-adrenergic blocker that also enhances nitric oxide bioavailability via the L-arginine-nitric oxide pathway, leading to vasodilation and decreased peripheral vascular resistance. It is marketed in Europe for the treatment of hypertension and heart failure and is currently being reviewed for use in the US by the Food and Drug Administration. Nebivolol appears to be well tolerated with an adverse event profile that is at least similar, if not better, than that of other beta-adrenergic blockers. Studies suggest that long-term therapy with nebivolol improves left ventricular function, exercise capacity, and clinical endpoints of death and cardiovascular hospital admissions in patients with stable heart failure. To date, it is one of the only beta-adrenergic blockers that have been exclusively studied in elderly patients. Additionally, the unique mechanism of action of nebivolol makes it a promising agent for treatment of chronic heart failure in high-risk patient populations, such as African Americans. This article will review the pharmacologic and pharmacokinetic properties of nebivolol as well as clinical studies assessing its efficacy for the treatment of heart failure.
Topics: Arginine; Benzopyrans; Chronic Disease; Drug Tolerance; Ethanolamines; Heart Failure; Humans; Nebivolol; Nitric Oxide
PubMed: 18078016
DOI: No ID Found -
Biomolecules Oct 2020Racemic chiral -heterocycles containing 2-arylchroman or 2-aryl-2-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were...
Racemic chiral -heterocycles containing 2-arylchroman or 2-aryl-2-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were synthesized with various substitution patterns of the aryl group by the cyclization of - or -3-aminoflavanone analogues. The 3-aminoflavanone precursors were obtained in a Neber rearrangement of oxime tosylates of flavanones, which provided the diastereomer as the major product and enabled the isolation of both the - and -diastereomers. The - and -aminoflavanones were utilized to prepare three diastereomers of 5-aryl-chromeno[4,3-b][1,]oxazines. Antiproliferative activity of the condensed heterocycles and precursors was evaluated against A2780 and WM35 cancer cell lines. For a 3-(-chloroacetylamino)-flavan-4-ol derivative, showing structural analogy with acyclic acid ceramidase inhibitors, 0.15 μM, 3.50 μM, and 6.06 μM IC values were measured against A2780, WM35, and HaCat cell lines, and apoptotic mechanism was confirmed. Low micromolar IC values down to 2.14 μM were identified for the thiazole- and pyrrole-condensed 2-chromene derivatives. Enantiomers of the condensed heterocycles were separated by HPLC using chiral stationary phase, HPLC-ECD spectra were recorded and TDDFT-ECD calculations were performed to determine the absolute configuration and solution conformation. Characteristic ECD transitions of the separated enantiomers were correlated with the absolute configuration and effect of substitution pattern on the HPLC elution order was determined.
Topics: Benzopyrans; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Cytostatic Agents; Female; Flavonoids; Heterocyclic Compounds; Humans; Molecular Conformation; Molecular Structure; Morpholines; Ovarian Neoplasms; Stereoisomerism
PubMed: 33092128
DOI: 10.3390/biom10101462 -
Molecules (Basel, Switzerland) May 2021Black, brown, and light peat and sapropel were analyzed as natural sources of organic and humic substances. These specific substances are applicable in industry,...
Black, brown, and light peat and sapropel were analyzed as natural sources of organic and humic substances. These specific substances are applicable in industry, agriculture, the environment, and biomedicine with well-known and novel approaches. Analysis of the organic compounds fulvic acid, humic acid, and humin in different peat and sapropel extracts from Lithuania was performed in this study. The dominant organic compound was bis(tert-butyldimethylsilyl) carbonate, which varied from 6.90% to 25.68% in peat extracts. The highest mass fraction of malonic acid amide was in the sapropel extract; it varied from 12.44% to 26.84%. Significant amounts of acetohydroxamic, lactic, and glycolic acid derivatives were identified in peat and sapropel extracts. Comparing the two extraction methods, it was concluded that active maceration was more efficient than ultrasound extraction in yielding higher amounts of organic compounds. The highest amounts of fulvic acid (1%) and humic acid and humin (15.3%) were determined in pure brown peat samples. This research on humic substances is useful to characterize the peat of different origins, to develop possible aspects of standardization, and to describe potential of the chemical constituents.
Topics: Alkalies; Benzopyrans; Gas Chromatography-Mass Spectrometry; Humic Substances; Soil
PubMed: 34069989
DOI: 10.3390/molecules26102995 -
Molecules (Basel, Switzerland) Feb 2018Herb-drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has...
Herb-drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of (Saururacease), possesses anti-oxidant, anti-inflammatory, and anti-viral activities. In pharmacokinetics of sauchinone, sauchinone is highly distributed to the liver, forming extensive metabolites of sauchinone via UGTs in the liver. Thus, we investigated whether sauchinone inhibited UGTs to explore potential of sauchinone-drug interactions. In human liver microsomes (HLMs), sauchinone inhibited activities of UGT1A1, 1A3, 1A6, and 2B7 with IC values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with values of 1.08 and 0.524 μM, respectively. In in vivo interaction study using mice, sauchinone inhibited UGT2B7-mediated zidovudine metabolism, resulting in increased systemic exposure of zidovudine when sauchinone and zidovudine were co-administered together. Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations.
Topics: Animals; Benzopyrans; Dioxoles; Drug Interactions; Glucuronosyltransferase; Humans; Male; Mice; Microsomes, Liver; Plant Extracts; Thermodynamics; Tracheophyta; Zidovudine
PubMed: 29425147
DOI: 10.3390/molecules23020366 -
Molecules (Basel, Switzerland) Dec 2017Nakai (AGN) is a crucial oriental medicinal herb that grows especially in Korea and the Far-East countries. It contains chemically active compounds like... (Review)
Review
Natural Korean Medicine Dang-Gui: Biosynthesis, Effective Extraction and Formulations of Major Active Pyranocoumarins, Their Molecular Action Mechanism in Cancer, and Other Biological Activities.
Nakai (AGN) is a crucial oriental medicinal herb that grows especially in Korea and the Far-East countries. It contains chemically active compounds like pyranocoumarins, polyacetylenes and essential oils, which might be useful for treatment of several chronic diseases. It has been used for centuries as a traditional medicine in Southeast Asia, but in Western countries is used as a functional food and a major ingredient of several herbal products. The genus is also known as 'female ginseng' due to its critical therapeutic role in female afflictions, such as gynecological problems. However, it is well-documented that the AGN pyranocoumarins may play vital beneficial roles against cancer, neurodisorders, inflammation, osteoporosis, amnesia, allergies, depression, fungi, diabetes, ischemia, dermatitis, reactive oxygen species (ROS) and androgen. Though numerous studies revealed the role of AGN pyranocoumarins as therapeutic agents, none of the reviews have published their molecular mechanism of action. To the best of our knowledge, this would be the first review that aims to appraise the biosynthesis of AGN's major active pyranocoumarins, discuss effective extraction and formulation methods, and detail the molecular action mechanism of decursin (D), decursinol angelate (DA) and decursinol (DOH) in chronic diseases, which would further help extension of research in this area.
Topics: Angelica; Angelica sinensis; Animals; Antineoplastic Agents, Phytogenic; Benzopyrans; Butyrates; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Liquid-Liquid Extraction; Medicine, Korean Traditional; Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal; Pyranocoumarins; Rodentia
PubMed: 29215592
DOI: 10.3390/molecules22122170 -
Chemical & Pharmaceutical Bulletin 2020A series of 2-(N-cyclicamino)chromone derivatives (1a-4c) and 3-(N-cyclicamino)chromone derivatives (5a-8c) were synthesized, and their monoamine oxidase (MAO) A and B...
A series of 2-(N-cyclicamino)chromone derivatives (1a-4c) and 3-(N-cyclicamino)chromone derivatives (5a-8c) were synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were studied as part of a structure-activity relationship investigation. Compounds 1a-4c showed no remarkable inhibition for MAO-A or MAO-B, whereas compounds 5a-8c (with a few exceptions) showed significant and selective inhibition of MAO-B. Of these compounds, 7c, 7-methoxy-3-(4-phenyl-1-piperazinyl)-4H-1-benzopyran-4-one inhibited MAO-B the most potently and selectively, having IC of 15 nM and an MAO-B selectivity index of more than 6700; c.f, 50 nM and 2000, respectively, for safinamide. The mode of inhibition of 7c to MAO-B was competitive and reversible. Considering the IC values and selectivity indices of the other synthetic compounds, the presence of the methoxy group on the chromone ring (R) of 7c seemed to increase MAO-B inhibition. Molecular docking analysis also supports this hypothesis. Our results suggest that 3-(N-cyclicamino)chromones are useful lead compounds for the development of MAO-B inhibitors.
Topics: Benzopyrans; Binding Sites; Catalytic Domain; Chromones; Inhibitory Concentration 50; Kinetics; Molecular Docking Simulation; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Structure-Activity Relationship
PubMed: 33132375
DOI: 10.1248/cpb.c20-00579