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European Journal of Heart Failure Sep 2015
Topics: Biphenyl Compounds; Female; Heart Failure; Humans; Male; Stroke Volume; Tetrazoles
PubMed: 26331780
DOI: 10.1002/ejhf.334 -
Angewandte Chemie (International Ed. in... Mar 2020A simple and efficient nitrile-directed meta-C-H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of...
A simple and efficient nitrile-directed meta-C-H olefination, acetoxylation, and iodination of biaryl compounds is reported. Compared to the previous approach of installing a complex U-shaped template to achieve a molecular U-turn and assemble the large-sized cyclophane transition state for the remote C-H activation, a synthetically useful phenyl nitrile functional group could also direct remote meta-C-H activation. This reaction provides a useful method for the modification of biaryl compounds because the nitrile group can be readily converted to amines, acids, amides, or other heterocycles. Notably, the remote meta-selectivity of biphenylnitriles could not be expected from previous results with a macrocyclophane nitrile template. DFT computational studies show that a ligand-containing Pd-Ag heterodimeric transition state (TS) favors the desired remote meta-selectivity. Control experiments demonstrate the directing effect of the nitrile group and exclude the possibility of non-directed meta-C-H activation. Substituted 2-pyridone ligands were found to be key in assisting the cleavage of the meta-C-H bond in the concerted metalation-deprotonation (CMD) process.
Topics: Biphenyl Compounds; Density Functional Theory; Molecular Structure
PubMed: 31943648
DOI: 10.1002/anie.201915624 -
Medicina (Kaunas, Lithuania) Feb 2023Combination therapy improves the effect of chemotherapy on tumor cells. Magnolol, used in treating gastrointestinal disorders, has been shown to have anti-cancer...
Combination therapy improves the effect of chemotherapy on tumor cells. Magnolol, used in treating gastrointestinal disorders, has been shown to have anti-cancer properties. We investigated the synergistic effect of cisplatin and magnolol on the viability and maintenance of MKN-45 gastric cancer cells. The toxicity of magnolol and/or cisplatin was determined using the MTT technique. The trypan blue method was used to test magnolol and/or cisplatin's effect on MKN-45 cell growth. Crystal violet staining was used to assess the treated cells' tendency for colony formation. The expression of genes linked to apoptosis, cell cycle arrest, and cell migration was examined using the qPCR method. According to MTT data, using magnolol and/or cisplatin significantly reduced cell viability. The ability of the treated cells to proliferate and form colonies was also reduced considerably. Magnolol and/or cisplatin treatment resulted in a considerable elevation in expression. However, the level of expression was dramatically reduced. and expression levels were significantly increased in the treated cells, while expression was significantly reduced. These findings show that magnolol has a remarkable anti-tumor effect on MKN-45 cells. In combination with cisplatin, magnolol may be utilized to overcome cisplatin resistance in gastric cancer cells.
Topics: Humans; Stomach Neoplasms; Cisplatin; Lignans; Biphenyl Compounds; Apoptosis; Cell Proliferation; Cell Line, Tumor
PubMed: 36837487
DOI: 10.3390/medicina59020286 -
Asian Pacific Journal of Tropical... Jan 2014To investigate the antioxidant efficacy of a biologically active diterpenoid compound sugiol isolated from Metasequoia glyptostroboides (M. glyptostroboides) in various...
OBJECTIVE
To investigate the antioxidant efficacy of a biologically active diterpenoid compound sugiol isolated from Metasequoia glyptostroboides (M. glyptostroboides) in various antioxidant models.
METHODS
An abietane type diterpenoid sugiol, isolated from ethyl acetate extract of M. glyptostroboides cones, was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl radicals.
RESULTS
The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities. Consequently, the sugiol exerted lipid peroxidation inhibitory effect by 76.5% as compared to α-tocopherol (80.13%) and butylated hydroxyanisole (76.59%). In addition, the sugiol had significant scavenging activities of 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%, 72.42%, 72.99% and 85.04%, when compared to the standard compound ascorbic acid (81.69%, 74.62%, 73.00% and 73.79%) and α-tocopherol/butylated hydroxyanisole (84.09%, 78.61%, 74.45% and 70.02%), respectively.
CONCLUSIONS
These findings justify the biological and traditional uses of M. glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.
Topics: Analysis of Variance; Animals; Antioxidants; Biphenyl Compounds; Brain Chemistry; Cattle; Cupressaceae; Diterpenes; Free Radical Scavengers; Lipid Peroxidation; Phospholipids; Picrates; Seeds
PubMed: 24418075
DOI: 10.1016/S1995-7645(13)60183-2 -
Bioorganic & Medicinal Chemistry Letters Sep 2017Heat Shock Protein 90 (Hsp90) is a molecular chaperone under clinical investigation for the treatment of neurodegenerative diseases and cancer. Neuroprotective Hsp90...
Heat Shock Protein 90 (Hsp90) is a molecular chaperone under clinical investigation for the treatment of neurodegenerative diseases and cancer. Neuroprotective Hsp90 C-terminal inhibitors (novologues) contain a biaryl ring system, and include KU-596, which was modified and investigated for potential anti-cancer activity. Incorporation of a benzamide group onto the biaryl novologues in lieu of the acetamide yielded compounds that manifest anti-cancer activity. Further exploration of the central phenyl ring led to compounds with enhanced anti-proliferative activity. The design, synthesis, and evaluation of these new analogs against breast and prostate cancer cell lines is reported herein, where it was found that 8b and 10 manifest potent anti-proliferative activity and a robust degradation of Hsp90 client-dependent proteins.
Topics: Antineoplastic Agents; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HSP90 Heat-Shock Proteins; Humans; Models, Molecular; Molecular Structure; Structure-Activity Relationship
PubMed: 28844386
DOI: 10.1016/j.bmcl.2017.07.030 -
Annals of Clinical Microbiology and... Oct 2010The aim of this study was to isolate and identify the antifungal compounds from the extracts of Schinus terebinthifolius (Anacardiaceae) against clinical isolates of the...
BACKGROUND
The aim of this study was to isolate and identify the antifungal compounds from the extracts of Schinus terebinthifolius (Anacardiaceae) against clinical isolates of the pathogenic fungus Paracoccidioides brasiliensis.
METHODS
The hexane and dichlomethane fractions from leaves and stems of S. terebinthifolius were fractionated using several chromatography techniques to afford four compounds.
RESULTS
The compounds isolated from S. terebinthifolius were identified as schinol (1), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (2), quercetin (3), and kaempferol (4). Compounds 1 and 2 were active against different strains of P. brasiliensis, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound 1 with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. terebinthifolius were not able to inhibit cell wall synthesis or assembly using the sorbitol assay.
CONCLUSION
This work reveals for the first time the occurrence of compound 2 and discloses activity of compounds 1 and 2 against several clinical isolates of P. brasiliensis. These results justify further studies to clarify the mechanisms of action of these compounds.
Topics: Anacardiaceae; Antifungal Agents; Biphenyl Compounds; Itraconazole; Microbial Sensitivity Tests; Paracoccidioides; Plant Extracts; Triterpenes
PubMed: 20939907
DOI: 10.1186/1476-0711-9-30 -
Women's Health (London, England) Nov 2015Odanacatib represents a novel treatment option in the approach of postmenopausal women. Postmenopausal women with osteoporosis experience a disturbance in bone... (Review)
Review
Odanacatib represents a novel treatment option in the approach of postmenopausal women. Postmenopausal women with osteoporosis experience a disturbance in bone remodeling wherein bone resorption exceeds bone formation. Cathepsin K is a lysosomal cysteine protease found primarily in osteoclasts that plays a major role in the breakdown of bone via its collagenase properties. Targeting a new area of pathophysiology, odanacatib inhibits cathepsin K to reduce bone resorption while preserving bone formation. Phase II and III trials have shown efficacy in increasing bone mineral density in the target treatment group. Overall, safety studies have found odanacatib to be well-tolerated and comparable to placebo; however, some imbalances in adverse events have been observed in the Phase III trials. Current and future studies will analyze the long-term ability of odanacatib in preventing bone fracture.
Topics: Biphenyl Compounds; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Bone and Bones; Cathepsin K; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal
PubMed: 26344800
DOI: 10.2217/whe.15.39 -
Bioorganic & Medicinal Chemistry Aug 2013A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino...
A series of macrocyclic biphenyl tetraoxazoles was synthesized. The latter stages of the synthetic approach allowed for the addition of varied N-protected α-amino acids, which were subsequently deprotected and condensed to provide the desired macrocycles. Improved yields could be realized in the macrocyclization step of their synthesis relative to other macrocyclic G-quadruplex stabilizers. These 24-membered macrocycles were evaluated for their ability to stabilize G-quadruplex DNA and for their relative cytotoxicity against human tumor cells. These biphenyl tetraoxazoles were not strong ligands for G-quadruplex DNA relative to other macrocyclic polyoxazoles. This reduced stabilizing potential did correlate with their comparatively lower cytotoxic activity as observed in the human tumor cell lines, RPMI 8402 and KB3-1. These studies provide useful insights into the conformational requirements for the development of selective and more potent G-quadruplex ligands.
Topics: Antineoplastic Agents; Biphenyl Compounds; Cell Line, Tumor; G-Quadruplexes; Humans; Macrocyclic Compounds; Models, Molecular; Molecular Structure; Oxazoles
PubMed: 23787291
DOI: 10.1016/j.bmc.2013.05.033 -
BMC Complementary and Alternative... Sep 2017Tinospora cordifolia (Guduchi or Amrita) is an important drug of Ayurvedic System of Medicine and found mention in various classical texts for the treatment of diseases...
BACKGROUND
Tinospora cordifolia (Guduchi or Amrita) is an important drug of Ayurvedic System of Medicine and found mention in various classical texts for the treatment of diseases such as jaundice, fever, diabetes, cancer and skin disease etc. In view of its traditional claims, antioxidant and anti-proliferative activities were evaluated in the present study.
METHODS
Ethanol extract (TCE) and subsequent petroleum ether (TCP), dichloromethane (TCD), n-Butanol (TCB) and aqueous (TCA) fractions of were prepared from stems of T cordifolia. Total phenolic, flavonoid content and anti-oxidant activity was assessed by different methods. Anti-proliferative activity was assessed in cervical carcinoma (HeLa) cell lines by MTT and SRB assay.
RESULTS
Ethanol extract and n-butanol fractions shown to be superior in their scavenging activity in all the tested methods. n-butanol fractions shown antioxidant activity with an IC of 14.81 ± 0.53, 29.48 ± 2.23, 58.20 ± 0.70 and 21.17 ± 1.19 μg/mL by DPPH, ABTS, Nitric oxide and iron chelating activities respectively. Anti-proliferative activity results demonstrates that the TCD and ethanol extract of T cordifolia exhibits potent cytotoxic effect against HeLa with an IC of 54.23 ± 0.94 μg/mL and 101.26 ± 1.42 μg/mL respectively by MTT assay; and with an IC of 48.91 ± 0.33 μg/mL and 87.93 ± 0.85 μg/mL respectively by SRB assay.
CONCLUSION
The outcomes of the present study support the fact that T Cordifolia is a promising source of antioxidant agent and propose its further investigation. Moreover, dichloromethane fraction of T cordifolia shown to be the most potent anti-proliferative fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.
Topics: Antioxidants; Berberine; Biphenyl Compounds; Cell Proliferation; HeLa Cells; Humans; Picrates; Plant Extracts; Tinospora
PubMed: 28893230
DOI: 10.1186/s12906-017-1953-3 -
Biochimica Et Biophysica Acta.... May 2017Electrochemical impedance techniques and fluorescence spectroscopic methods have been applied to the study of the interaction of ortho (o)-, meta (m)- and para (p)-Cl-,...
Electrochemical impedance techniques and fluorescence spectroscopic methods have been applied to the study of the interaction of ortho (o)-, meta (m)- and para (p)-Cl-, o-, m- and p-HO-, p-HCO-, p-HC-, p-NC- and p-OS- substituted biphenyls (BPs) with Hg supported dioleoyl phosphatidylcholine (DOPC) monolayers and DOPC vesicles. Non-planar o-substituted BPs exhibit the weakest interactions whereas planar p-substituted BPs interact to the greatest extent with the DOPC layers. The substituted BP/DOPC monolayer and bilayer interaction depends on the effect of the substituent on the aromatic electron density, which is related to the substituents' mesomeric Hammetts constants. Substituted BPs with increased ring electron density do not increase the DOPC monolayer thickness on Hg and penetrate the DOPC vesicle membranes to the greatest extent. Substituted BPs with lower ring electron density can cause an increase in the monolayer's thickness on Hg depending on their location and they remain in the interfacial and superficial layer of the free standing DOPC membranes. Quantum mechanical calculations correlate the binding energy between the substituted BP rings and methyl acetate, as a model for the -CH-(CO)O-CH- fragment of a DOPC molecule, with the location of BPs within the DOPC monolayer.
Topics: Biphenyl Compounds; Electric Impedance; Electrochemical Techniques; Lipid Bilayers; Phosphatidylcholines; Spectrometry, Fluorescence
PubMed: 28130013
DOI: 10.1016/j.bbamem.2017.01.023