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Journal of Natural Products Oct 2017Operationally simple, stereocontrolled semisyntheses of the anticancer rotenoids elliptone and 12aβ-hydroxyelliptone, isolated from Derris elliptica and Derris...
Operationally simple, stereocontrolled semisyntheses of the anticancer rotenoids elliptone and 12aβ-hydroxyelliptone, isolated from Derris elliptica and Derris trifoliata, respectively, are described. Inspired by the work of Singhal, elliptone was prepared from rotenone via a dihydroxylation-oxidative cleavage, chemoselective Baeyer-Villiger oxidation, and acid-catalyzed elimination sequence. Elaboration of elliptone to 12aβ-hydroxyelliptone was achieved via a diastereoselective chromium-mediated Étard-like hydroxylation. The semisynthesis of elliptone constitutes an improvement over previous methods in terms of safety, scalability, and yield, while the first synthesis of 12aβ-hydroxyelliptone is also described.
Topics: Benzopyrans; Derris; Molecular Structure; Rotenone; Stereoisomerism
PubMed: 29039664
DOI: 10.1021/acs.jnatprod.7b00527 -
Journal of the American Chemical Society Dec 2022Mechanophores are powerful molecular tools used to track bond rupture and characterize mechanical damage in polymers. The majority of mechanophores are known to respond...
Mechanophores are powerful molecular tools used to track bond rupture and characterize mechanical damage in polymers. The majority of mechanophores are known to respond to external stresses, and we report in this study the first precedent of a mechanochemical response to internal, residual stresses that accumulate during polymer vitrification. While internal stress is intrinsic to polymers that can form solids, we demonstrate that it can dramatically affect the mechanochemistry of spiropyran probes and alter their intramolecular isomerization barriers by up to 70 kJ mol. This new behavior of spiropyrans (SPs) enables their application for analysis of internal stresses distribution and their mechanochemical characterization on the molecular level. Spectroscopy and imaging based on SP mechanochemistry showed high topological sensitivity and allowed us to discern different levels of internal stress impacting various locations along the polymer chain. The nature of the developed technique allows for wide-field imaging of stress heterogeneities in polymer samples of irregular shapes and dimensions, making it feasible to directly observe molecular-level manifestations of mechanical stresses that accompany the formation of a vast number of solid polymers.
Topics: Polymers; Benzopyrans; Indoles; Nitro Compounds
PubMed: 36509594
DOI: 10.1021/jacs.2c11280 -
Journal of Chemical Ecology Dec 2017Bacteria and fungi in shared environments compete with one another for common substrates, and this competition typically involves microbially-produced small molecules....
Bacteria and fungi in shared environments compete with one another for common substrates, and this competition typically involves microbially-produced small molecules. An investigation of one shared environmental niche, the carton material of the Formosan subterranean termite Coptotermes formosanus, identified the participants on one of these molecular exchanges. Molecular characterization of several termite-associated actinobacteria strains identified eleven known antimicrobial metabolites that may aid in protecting the C. formosanus colony from pathogenic fungal infections. One particular actinobacterial-derived small molecule, bafilomycin C1, elicited a strong chemical response from Trichoderma harzianum, a common soil saprophyte. Upon purification and structure elucidation, three major fungal metabolites were identified, t22-azaphilone, cryptenol, and homodimericin A. Both t22-azaphilone and homodimericin A are strongly upregulated, 123- and 38-fold, respectively, when exposed to bafilomycin C1, suggesting each play a role in defending T. harzianum from the toxic effect of bafilomycin C1.
Topics: Actinobacteria; Animals; Anti-Infective Agents; Benzopyrans; Isoptera; Macrolides; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Pigments, Biological; Polyketides; Streptomyces; Trichoderma
PubMed: 29134406
DOI: 10.1007/s10886-017-0900-6 -
Molecules (Basel, Switzerland) Oct 2023Traditional medicinal plants have been used for decades in folk medicines in the treatment and management of several ailments and diseases including diabetes, pain,... (Review)
Review
Traditional medicinal plants have been used for decades in folk medicines in the treatment and management of several ailments and diseases including diabetes, pain, ulcers, cancers, and wounds, among others. This study focused on the phytochemical and antidiabetic activity of the commonly used antidiabetic medicinal species in Kenya. Phytochemical profiling of these species revealed flavonoids and terpenoids as the major chemical classes reported which have been linked with strong biological activities against the aforementioned diseases, among others. However, out of the selected twenty-two species, many of the natural product isolation studies have focused on only a few species, as highlighted in the study. All of the examined crude extracts from thirteen antidiabetic species demonstrated strong antidiabetic activities by inhibiting α-glucosidase and α-amylase among other mechanisms, while nine are yet to be evaluated for their antidiabetic activities. Isolated compounds S-Methylcysteine sulfoxide, quercetin, alliuocide G, 2-(3,4-Dihydroxybenzoyl)-2,4,6-trihydroxy-3 (2)-benzofuranone, Luteolin-7--D-glucopyranoside, quercetin, 1,3,11-Trihydroxy-9-(3,5,7-trihydroxy-4-1-benzopyran-7-on-2-yl)-5-(3,4-dihydroxy-phenyl)-5,6,11-hexahydro-5,6,11-trioxanaphthacene-12-one and [1,3,11-Trihydroxy-9-(3,5,7-trihydroxy-4-1-benzopyran-7-on-2-yl)-5-(3,4-dihydroxy-phenyl)-5,6,11-hexahydro-5,6,11-trioxanaphthacene-12-one]-4'--D-gluco-pyranoside from have been found to exhibit significant antidiabetic activities. With the huge number of adults living with diabetes in Kenya and the available treatment methods being expensive yet not so effective, this study highlights alternative remedies by documenting the commonly used antidiabetic medicinal plants. Further, the study supports the antidiabetic use of these plants with the existing pharmacological profiles and highlights research study gaps. Therefore, it is urgent to conduct natural products isolation work on the selected antidiabetic species commonly used in Kenya and evaluate their antidiabetic activities, both in vitro and in vivo, to validate their antidiabetic use and come up with new antidiabetic drugs.
Topics: Plants, Medicinal; Hypoglycemic Agents; Quercetin; Kenya; Plant Extracts; Diabetes Mellitus; Benzopyrans; Phytochemicals
PubMed: 37894680
DOI: 10.3390/molecules28207202 -
Chemical & Pharmaceutical Bulletin 2012New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b,...
New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.
Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Benzopyrans; Binding Sites; Carrageenan; Catalytic Domain; Computer Simulation; Cyclooxygenase 2; Diclofenac; Dinoprostone; Disease Models, Animal; Edema; Gene Expression Regulation; Male; Rats; Rats, Wistar
PubMed: 22223382
DOI: 10.1248/cpb.60.110 -
Cephalalgia : An International Journal... Nov 2009Migraine is a neurovascular disorder characterized by recurrent episodic headaches, and is caused by abnormal processing of sensory information due to peripheral and/or... (Review)
Review
Migraine is a neurovascular disorder characterized by recurrent episodic headaches, and is caused by abnormal processing of sensory information due to peripheral and/or central sensitization. The exact pathophysiological mechanism underlying migraine is not fully understood; however, cortical spreading depression (CSD) is thought to provide the basis for migraine aura and may serve as a trigger of migraine pain. CSD depends on neuronal-glial cell communication, which is mediated by intercellular transfer of messengers through connexin-containing gap junctions, as well as messengers released into the extracellular space by non-junctional connexin-containing hemichannels. These processes are believed to be important in peripheral sensitization within the trigeminal ganglion and to lead to central sensitization. The novel benzopyran compound tonabersat binds selectively to a unique site in the brain. In preclinical studies, tonabersat markedly reduced CSD and CSD-associated events and inhibited gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. Together, these findings suggest that tonabersat should have clinical application in preventing migraine attacks.
Topics: Analgesics; Animals; Benzamides; Benzopyrans; Brain; Cortical Spreading Depression; Gap Junctions; Humans; Migraine Disorders
PubMed: 19723120
DOI: 10.1111/j.1468-2982.2009.01976.x -
The Journal of Biological Chemistry 2021Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic...
Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic drugs have limited efficacy and/or carry the risk of ventricular proarrhythmia. The cardiac acetylcholine activated inwardly rectifying K current (I), composed of Kir3.1/Kir3.4 heterotetrameric and Kir3.4 homotetrameric channel subunits, is one of the best validated atrial-specific ion channels. Previous research pointed to a series of benzopyran derivatives with potential for treatment of arrhythmias, but their mechanism of action was not defined. Here, we characterize one of these compounds termed Benzopyran-G1 (BP-G1) and report that it selectively inhibits the Kir3.1 (GIRK1 or G1) subunit of the K channel. Homology modeling, molecular docking, and molecular dynamics simulations predicted that BP-G1 inhibits the I channel by blocking the central cavity pore. We identified the unique F137 residue of Kir3.1 as the critical determinant for the I-selective response to BP-G1. The compound interacts with Kir3.1 residues E141 and D173 through hydrogen bonds that proved critical for its inhibitory activity. BP-G1 effectively blocked the I channel response to carbachol in an in vivo rodent model and displayed good selectivity and pharmacokinetic properties. Thus, BP-G1 is a potent and selective small-molecule inhibitor targeting Kir3.1-containing channels and is a useful tool for investigating the role of Kir3.1 heteromeric channels in vivo. The mechanism reported here could provide the molecular basis for future discovery of novel, selective I channel blockers to treat atrial fibrillation with minimal side effects.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzopyrans; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Ion Channel Gating; Mice; Molecular Docking Simulation
PubMed: 33713702
DOI: 10.1016/j.jbc.2021.100535 -
Molecular Imaging and Biology Dec 2019To develop a tool to measure the pH at the surfaces of individual cells.
PURPOSE
To develop a tool to measure the pH at the surfaces of individual cells.
PROCEDURES
The SNARF pH-sensitive dye was conjugated to a pHLIP® peptide (pH-Low Insertion Peptide) that binds cellular membranes in tumor spheroids. A beam splitter allows simultaneous recording of two images (580 and 640 nm) by a CCD camera. The ratio of the two images is converted into a pH map resolving single spheroid cells. An average pH for each cell is calculated and a pH histogram is derived.
RESULTS
Surface pH depends on cellular glycolytic activity, which was varied by adding glucose or deoxy-glucose. Glucose was found to decrease the surface pH relative to the pH of the bulk solution. The surface pH of metastatic cancer cells was lower than that of non-metastatic cells indicating a higher glycolytic activity.
CONCLUSIONS
Our method allows cell surface pH measurement and its correlation with cellular glycolytic activity.
Topics: Benzopyrans; Cell Line, Tumor; Cell Membrane; Humans; Hydrogen-Ion Concentration; Image Processing, Computer-Assisted; Membrane Proteins; Neoplasm Metastasis; Neoplasms
PubMed: 30989440
DOI: 10.1007/s11307-019-01335-4 -
Molecules (Basel, Switzerland) Dec 2020Two new epimeric bibenzylated monoterpenes machaerifurogerol () and 5--machaerifurogerol (), and four known isoflavonoids (+)-vestitol (), 7--methylvestitol (),...
Antimicrobial Constituents from Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant , Vancomycin-Resistant , and Permeabilized Gram-Negative Pathogens.
Two new epimeric bibenzylated monoterpenes machaerifurogerol () and 5--machaerifurogerol (), and four known isoflavonoids (+)-vestitol (), 7--methylvestitol (), (+)-medicarpin (), and 3,8-dihydroxy-9-methoxypterocarpan () were isolated from Pers. This plant was previously assigned as Spruce, from which machaeriols A-D (-) and machaeridiols A-C (-) were reported, and all were then re-isolated, except the minor compound , for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture + was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant (VRE 700221) and . (VRE 51299) and vancomycin-sensitive (VSE 29212). Compounds - and - were found to be more potent against MRSA 1708, and , , and against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols ( or ) and machaeridiols ( or ), which exhibited a strong synergistic activity of + (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC's, compared to , against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds + , , , and showed activity in the range of 0.5-8 µg/mL for two strains of , 2-16 µg/mL against PAO1, and 2 µg/mL against NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of .
Topics: Anti-Bacterial Agents; Benzopyrans; Fabaceae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Vancomycin-Resistant Enterococci
PubMed: 33352963
DOI: 10.3390/molecules25246000 -
Organic Letters Aug 2016The synthesis of a small-molecule dyad consisting of a far-red-emitting silicon rhodamine dye that is covalently linked to a photochromic spironaphthothiopyran unit,...
The synthesis of a small-molecule dyad consisting of a far-red-emitting silicon rhodamine dye that is covalently linked to a photochromic spironaphthothiopyran unit, which serves as a photoswitchable quencher, is reported. This system can be switched reversibly between the fluorescent and nonfluorescent states using visible light at wavelengths of 405 and 630 nm, respectively, and it works effectively in aqueous solution. Live-cell imaging demonstrates that this dyad has several desirable features, including excellent membrane permeability, fast and reversible modulation of fluorescence by visible light, and good contrast between the bright and dark states.
Topics: Benzopyrans; Cell Survival; Fluorescent Dyes; Indoles; Molecular Structure; Nitro Compounds; Optical Imaging; Photochemical Processes; Rhodamines
PubMed: 27456166
DOI: 10.1021/acs.orglett.6b01717