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Planta Medica Nov 2018and bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their... (Review)
Review
and bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. and genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe.
Topics: Animals; Biphenyl Compounds; Drug Interactions; Humans; Lignans; Magnolia; Mutagenicity Tests; Plant Extracts; Tissue Distribution
PubMed: 29925102
DOI: 10.1055/a-0642-1966 -
Analytical Sciences : the International... 2018We report on a paper-based 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) assay for a simple, inexpensive, low reagent and sample consumption and high throughput...
We report on a paper-based 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) assay for a simple, inexpensive, low reagent and sample consumption and high throughput analysis of antioxidant activity. The paper-based device was fabricated using a lamination method to create a 5-mm in diameter circular test zone that was embedded with a DPPH reagent. The analysis was carried out in one-step by dropping an antioxidant/sample onto the test zone. After reduction by the antioxidant, the DPPH radicals become stable DPPH molecules, resulting in a change in color from deep violet to pale yellow. The violet color intensity of DPPH was inversely proportional to the antioxidant activity of the samples, and was measured using imaging software. A high precision and a low limit of detection were found in the analysis of six standard antioxidants including gallic acid, trolox, ascorbic acid, caffeic acid, vanilliic acid and quercetin. The device was then validated against the traditional spectrophotometric DPPH assay by analyzing the antioxidant activity of 7 tea samples. The results showed no significant difference for gallic acid equivalent for all 7 samples obtained from the two methods at the 95% confidence level, indicating that the developed method was reliable for antioxidant activity analysis of real samples. Finally, the paper-based DPPH device was found to be stable over 10 days when stored in a refrigerator (2 - 4°C), making it an easy-to-use device for end-users.
Topics: Antioxidants; Biphenyl Compounds; Paper; Picrates; Refrigeration
PubMed: 29998961
DOI: 10.2116/analsci.18P014 -
Nature Jun 2005Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many...
Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.
Topics: Animals; Antineoplastic Agents; Apoptosis; Biphenyl Compounds; Carcinoma, Small Cell; Cell Line, Tumor; Cytochromes c; Disease Models, Animal; Drug Synergism; Humans; Lymphoma; Magnetic Resonance Spectroscopy; Mice; Mitochondria; Models, Molecular; Neoplasms; Nitrophenols; Paclitaxel; Piperazines; Proto-Oncogene Proteins c-bcl-2; Structure-Activity Relationship; Sulfonamides; Survival Rate
PubMed: 15902208
DOI: 10.1038/nature03579 -
The New England Journal of Medicine Sep 2001Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria.
METHODS
A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level.
RESULTS
The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02).
CONCLUSIONS
Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria.
Topics: Adult; Aged; Albuminuria; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biphenyl Compounds; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Female; Humans; Hypertension; Irbesartan; Male; Middle Aged; Proportional Hazards Models; Tetrazoles
PubMed: 11565519
DOI: 10.1056/NEJMoa011489 -
ChemMedChem Nov 2022We identified 2,4-dinitro-biphenyl-based compounds as new inhibitors of leukotriene C synthase (LTC S) and 5-lipoxygenase-activating protein (FLAP), both members of the...
We identified 2,4-dinitro-biphenyl-based compounds as new inhibitors of leukotriene C synthase (LTC S) and 5-lipoxygenase-activating protein (FLAP), both members of the "Membrane Associated Proteins in Eicosanoid and Glutathione metabolism" (MAPEG) family involved in the biosynthesis of pro-inflammatory eicosanoids. By molecular docking we evaluated the putative binding against the targets of interest, and by applying cell-free and cell-based assays we assessed the inhibition of LTC S and FLAP by the small molecules at low micromolar concentrations. The present results integrate the previously observed inhibitory profile of the tested compounds against another MAPEG member, i. e., microsomal prostaglandin E synthase (mPGES)-1, suggesting that the 2,4-dinitro-biphenyl scaffold is a suitable molecular platform for a multitargeting approach to modulate pro-inflammatory mediators in inflammation and cancer treatment.
Topics: Molecular Docking Simulation; Glutathione Transferase; 5-Lipoxygenase-Activating Proteins; Biphenyl Compounds; Prostaglandin-E Synthases
PubMed: 36111583
DOI: 10.1002/cmdc.202200327 -
The Journal of Organic Chemistry Nov 2021In this work, we demonstrate that readily available conjugated bis-aryl cyclobutenones undergo photoelectrocyclization reactions to give the corresponding...
In this work, we demonstrate that readily available conjugated bis-aryl cyclobutenones undergo photoelectrocyclization reactions to give the corresponding dihydrophenanthrene cyclobutanones when exposed to 350 nm light, TFA, and TMSCl. We have also found that cyclobutenone electrocyclizations and cycloreversions are in equilibrium.
Topics: Biphenyl Compounds; Cyclobutanes
PubMed: 34586823
DOI: 10.1021/acs.joc.1c01809 -
BioMed Research International 2019Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated... (Review)
Review
Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from , has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-B/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Cardiovascular Agents; Drugs, Chinese Herbal; Humans; Lignans; MAP Kinase Signaling System; Magnolia; Medicine, Chinese Traditional; NF-E2-Related Factor 2; NF-kappa B; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Signal Transduction
PubMed: 31240205
DOI: 10.1155/2019/1847130 -
Drug Safety Feb 2019The hedgehog pathway, for which sonic hedgehog (Shh) is the most prominent ligand, is highly conserved and is tightly associated with embryonic development in a number... (Review)
Review
The hedgehog pathway, for which sonic hedgehog (Shh) is the most prominent ligand, is highly conserved and is tightly associated with embryonic development in a number of species. This pathway is also tightly associated with the development of several types of cancer, including basal cell carcinoma (BCC) and acute promyelocytic leukemia, among many others. Inactivating mutations in Patched-1 (PTCH1), leading to ligand-independent pathway activation, are frequent in several cancer types, but most prominent in BCC. This has led to the development of several compounds targeting this pathway as a cancer therapeutic. These compounds target the inducers of this pathway in Smoothened (SMO) and the GLI transcription factors, although targeting SMO has had the most success. Despite the many attempts at targeting this pathway, only three US FDA-approved drugs for cancers affect the Shh pathway. Two of these compounds, vismodegib and sonidegib, target SMO to suppress signaling from either PTCH1 or SMO mutations that lead to upregulation of the pathway. The other approved compound is arsenic trioxide, which can suppress this pathway at the level of the GLI proteins, although current evidence suggests it also has other targets. This review focuses on the safety and tolerability of these clinically approved drugs targeting the Shh pathway, along with a discussion on other Shh pathway inhibitors being developed.
Topics: Animals; Antineoplastic Agents; Biphenyl Compounds; Hedgehog Proteins; Humans; Myalgia; Neoplasms; Pyridines; Signal Transduction
PubMed: 30649745
DOI: 10.1007/s40264-018-0777-5 -
Bioorganic & Medicinal Chemistry Jun 2020The incorporation of nucleotides equipped with C-glycosidic aromatic nucleobases into DNA and RNA is an alluring strategy for a number of practical applications...
The incorporation of nucleotides equipped with C-glycosidic aromatic nucleobases into DNA and RNA is an alluring strategy for a number of practical applications including fluorescent labelling of oligonucleotides, expansion of the genetic alphabet for the generation of aptamers and semi-synthetic organisms, or the modulation of excess electron transfer within DNA. However, the generation of C-nucleoside containing oligonucleotides relies mainly on solid-phase synthesis which is quite labor intensive and restricted to short sequences. Here, we explore the possibility of constructing biphenyl-modified DNA sequences using enzymatic synthesis. The presence of multiple biphenyl-units or biphenyl residues modified with electron donors and acceptors permits the incorporation of a single dBphMP nucleotide. Moreover, templates with multiple abasic sites enable the incorporation of up to two dBphMP nucleotides, while TdT-mediated tailing reactions produce single-stranded DNA oligonucleotides with four biphenyl residues appended at the 3'-end.
Topics: Biphenyl Compounds; DNA; DNA-Directed DNA Polymerase; Humans; Molecular Structure; Oligonucleotides
PubMed: 32284226
DOI: 10.1016/j.bmc.2020.115487 -
International Journal of Molecular... May 2021Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of...
Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds-namely, compounds and -were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC values of 1.7 ± 0.5 μM for and 2.0 ± 0.7 μM for ) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound or , highlighted an arrest in the G2/M transition. Taking all this evidence together, and were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.
Topics: Antineoplastic Agents; Apoptosis; Biphenyl Compounds; Cell Cycle; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Melanoma; Signal Transduction; Skin Neoplasms; Structure-Activity Relationship; Melanoma, Cutaneous Malignant
PubMed: 34073232
DOI: 10.3390/ijms22115636