Synthesis, design, and antiproliferative evaluation of 6-(N-Substituted-methyl)pyrazolo[3,4-d]pyrimidines as the potent anti-leukemia agents.

Pyrazolopyrimidine derivatives, including pyrazolopyrimidines, 6-aminopyrazolopyrimidines, 6-[(formyloxy)methyl]pyrazolopyrimidines, 6-(hydroxymethyl)pyrazolopyrimidine, and 6-(aminomethyl)pyrazolopyrimidines have been successfully prepared and tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Among the tested pyrazolopyrimidine compounds, we found 6-aminopyrazolopyrimidines and 6-(aminomethyl)pyrazolopyrimidines with essential o-ClPh or p-ClPh substituted moieties on N-1 pyrazole ring exhibited the best IC inhibition activity for Jurkat cells. Furthermore, optimization of the SAR study on the C-6 position of pyrazolopyrimidine ring demonstrated that 6-(N-substituted-methyl)pyrazolopyrimidines 17b, 17d, and 19d possessed the significant IC inhibitory activity for the different leukemia cell lines, especially for Jurkat, K-562, and HL-60.

4,4-Diallyl curcumin bis(2,2-hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine-choline-deficient diet and Western diet mouse models.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4-diallyl curcumin bis(2,2-hydroxymethyl)propanoate, also known as 35e, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II, heat shock protein 60, and translocase of the outer mitochondrial membrane 20.

How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.

Induction of antioxidant proteins and phase 2 detoxifying enzymes that neutralize reactive electrophiles are important mechanisms for protection against carcinogenesis. Normal cells provide multifaceted pathways to tightly control NF-E2-related factor 2 (NRF2)-mediated gene expression in response to an assault by a range of endogenous and exogenous oncogenic molecules. Transient activation of NRF2 by its activators is able to induce ARE-mediated cytoprotective proteins which are essential for protection against various toxic and oxidative damages, and NRF2 activators thereby have efficacy in cancer chemoprevention.

Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma.

Several epidemiological studies have suggested that Epstein-Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry.

Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation.

Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option.

Identification of antiproliferative emodin analogues as inhibitors of epidermal growth factor receptor in cancer.

A series of emodin analogues have been demonstrated to exhibit potent antiproliferative activity in three human epidermal growth factor receptor 2 (HER2)‑overexpressing cell lines. However, in docking simulations, not all of these emodin analogues docked into the HER2 protein binding site. As the epidermal growth factor receptor (EFGR) and HER2 proteins are members of the ErbB family, the present study aimed to determine whether these anthraquinone derivatives exhibit potent antitumour bioactivity due to their inhibition of EGFR protein.

The Constituents of the Stems of and Their Bioactivities.

Fifty-five compounds were isolated from the fresh stems of , including 14 benzenoids, 11 triterpenes, nine steroids, five tocopherols, five chlorophylls, four flavonoids, two benzoquinones, two tannins, and three other compounds. Their structures were constructed by 1D and 2D nuclear magnetic resonance (NMR) and mass spectral data, and were also identified by a comparison of their spectral data with those reported in the literature. Among these isolates, 1,2-bis-(5--tocopheryl) ethane () was reported for the first time from natural sources.

Mechanistic Study of Tetrahydrofuran- acetogenins In Triggering Endoplasmic Reticulum Stress Response-apotoposis in Human Nasopharyngeal Carcinoma.

For past three decades, numerous studies have elucidated the antiproliferative effects of acetogenins in hopes of developing a new class of clinical anticancer agents. However, clear and definitive action mechanisms of acetogenins were less clarified. In the present study, three tetrahydrofuran (THF)-containing acetogenins were found to have potent and selective antiproliferative activity against human nasopharyngeal carcinoma (NPC) cell lines and their methotrexate-resistant counterparts.

Correction: Chan, Y.-Y., et al. The Constituents of Michelia compressa var. formosana and Their Bioactivities. Int. J. Mol. Sci. 2014, 15, 10926-10935.

The authors wish to make two changes to their published paper [1]. [..

The Inhibitory Mechanisms Study of 5,6,4'-Trihydroxy-7,3'-Dimethoxyflavone against the LPS-Induced Macrophage Inflammatory Responses through the Antioxidant Ability.

The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone (5-TDMF), was purified from a methanol extract of Anisomeles ovata. A pharmacological study of this compound suggests that 5-TDMF possesses potent free radical scavenging activity both in vitro and ex vivo.

WTC-01, a novel synthetic oxime-flavone compound, destabilizes microtubules in human nasopharyngeal carcinoma cells in vitro and in vivo.

Background And Purpose: Dynamic polymerization of microtubules is essential for cancer cell growth and metastasis, and microtubule-disrupting agents have become the most successful anti-cancer agents in clinical use. Besides their antioxidant properties, flavonoids also exhibit strong microtubule-disrupting activity and inhibit tumour growth. We have designed, synthesized and tested a series of oxime/amide-containing flavone derivatives.

Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators.

Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application.

Em08red, a dual functional antiproliferative emodin analogue, is a downregulator of ErbB2 expression and inducer of intracellular oxidative stress.

Expression of ErbB2 protein is inversely correlated with the prognosis in cancer patients. Consequently, strategies targeting ErbB2 remain an attractive option in treating several types of malignancies, including oral cancer. In addition, many studies have shown that emodin and emodin derivatives are able to inhibit growth of ErbB2-overexpressing tumor cells.

Genetic variants in the Hippo pathway predict biochemical recurrence after radical prostatectomy for localized prostate cancer.

While localized prostate cancer is potentially curative, many patients still show biochemical recurrence (BCR) after curative treatments such as radical prostatectomy (RP). The Hippo pathway has recently been shown to be an evolutionarily conserved regulator of tissue growth, and its perturbation can trigger tumorigenesis. We hypothesize that genetic variants of the Hippo pathway may influence clinical outcomes in localized prostate cancer patients.

The constituents of Michelia compressa var. formosana and their bioactivities.

Phytochemical investigation of the heartwood of Michelia compressa afforded forty-four compounds, which were identified by comparison of experimental and literature analytical and spectroscopic data. Some compounds were evaluated for their anti-inflammatory and anticancer bioactivities. The result showed that soemerine (1) and cyathisterol (2) exhibited significant nitric oxide (NO) inhibition, with IC50 values of 8.

Constituents of the roots of Clausena lansium and their potential anti-inflammatory activity.

Eight new carbazole alkaloids, claulamines C (1), D (2), and E (5) and clausenalines B-F (3, 4, 6-8), four new coumarins, clausemarins A-D (9-12), and 43 known compounds were isolated from the roots of Clausena lansium. The structures of the new compounds were established on the basis of 2D-NMR spectroscopic analysis, and their absolute configurations were established from their ECD spectra. The configuration of wampetin was revised as E using a NOESY experiment.

Synthesis and antiproliferative evaluation of amide-containing anthraquinone, xanthone, and carbazole.

Certain amide-containing anthraquinone, xanthone, and carbazole derivatives have been synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal carcinoma (NPC-TW01), lung carcinoma (NCI-H661), and leukemia (Jurkat). Among them, 2-(9,10-dioxo-9,10-dihydroanthracen-2-yloxy)-N-(naphthalen-2-yl)acetamide (13) was the most active against NPC-TW01 with an IC50 value of 2.62 µM while its xanthone and dibenzofuran counterparts, 14 and 15, were inactive with an IC50 value of 16.

Interaction of rhubarb and methotrexate in rats: in vivo and ex vivo approaches.

Rhubarb, the rhizome of Rheum palmatum L. (RP), is a popular herb used in Chinese medicine prescriptions. RP contains a variety of polyphenolic anthraquinones, such as aloe-emodin, rhein, emodin and chrysophanol.

Potential risk of mulberry-drug interaction: modulation on P-glycoprotein and cytochrome P450 3A.

Mulberry is a fruit containing polyphenol antioxidants. Cyclosporine (CSP), a potent immunosuppressant with a narrow therapeutic range, is widely used in transplant patients. This study investigated the effect of co-administration of mulberry on the bioavailability of CSP, a probe drug of P-glycoprotein (P-gp)/cytochrome P450 3A4 (CYP 3A4), in rats and relevant mechanisms.

Synthesis and antiproliferative activities of N-(naphthalen-2-yl)acetamide and N-(substituted phenyl)acetamide bearing quinolin-2(1H)-one and 3,4-dihydroquinolin-2(1H)-one derivatives.

Certain N-(naphthalen-2-yl)acetamide and N-(substituted phenyl)acetamide bearing quinolin-2(1H)-one and 3,4-dihydroquinolin-2(1H)-one derivatives have been synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal (NPC-TW01), lung carcinoma (H661), hepatoma (Hep3B), renal carcinoma (A498), and gastric cancer (MKN45). Among them, N-(naphthalen-2-yl)-2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yloxy)acetamide (18) was the most active against NPC-TW01 with an IC(50) value of 0.6 μM.

Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction.

The rhizome of Rheum palmatum (RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat.

St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats.

St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window.