Published in European Journal of Medicinal Chemistry in Oct 23, 2014
Here we describe the synthesis and biological activity of novel amino-pyrazolopyridines with anti-NF-κB and pro-apoptotic potential. α-Methylene ketones were used as a starting point for synthesis of amino-pyrazolopyridine 3. The alkylidene malononitriles 1 were obtained by the Knoevenagel reaction of ketones with malononitriles. Vilsmeier-Haack ...
Published in Cancer Letters in Sep 23, 2014
Cancer remains a major public health problem in our society. The development of potent novel anti-cancer drugs selective for tumor cells is therefore still required. Deregulation of the epigenetic machinery including DNA methylation, histone modifications and non-coding RNAs is a hallmark of cancer, which provides potential new therapeutic targets....
Published in Journal of Ethnopharmacology in Sep 23, 2014
The oil macerates of Hypericum perforatum L. (St. John's Wort=SJW) has a long history of medicinal use and SJW has been used in traditional medicine both orally and topically for centuries worldwide mainly for wound healing, ulcer and inflammation.
Published in European Journal of Medicinal Chemistry in Sep 23, 2014
A new series of chalcones, flavanones and flavones with methylenedioxy group at the 3',4' position in chalcone, 7,8 position in flavanones and flavones with mono-, di- and trimethoxy groups in the benzaldehyde ring have been assessed for their effect on proliferation, cytotoxic potential and apoptosis in human leukemia cells. Among the tested compo...
Published in Molecules in Sep 15, 2014
Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viabili...
Published in Bioorganic & Medicinal Chemistry Letters in Aug 23, 2014
Histone deacetylases (HDACs) are well-established, promising targets for anticancer therapy due to their critical role in cancer development. Accordingly, an increasing number of HDAC inhibitors displaying cytotoxic effects against cancer cells have been reported. Among them, a large panel of chemical structures was described including coumarin-con...
Published in Frontiers in Pharmacology in Jul 15, 2014
Glutathione S-transferases (GSTs) are phase II drug detoxifying enzymes that play an essential role in the maintenance of cell integrity and protection against DNA damage by catalyzing the conjugation of glutathione to a wide variety of exo- and endogenous electrophilic substrates. Glutathione S-transferase P1 (GSTP1), the gene encoding the pi-clas...
Published in Molecules in Jul 09, 2014
Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells a...
Published in Phytochemistry Reviews in Jul 07, 2014
The World Health Organization estimates that 4 billion people or 80% of the population use plants for curative purposes or for their natural health benefits. Accordingly, biodiversity is an important source of active natural products especially used in traditional medicine as healers transmitted knowledge of traditional usage of medicinal plants fr...
Published in Neoplasia in Jun 23, 2014
Increased proliferation rates as well as resistance to apoptosis are considered major obstacles for the treatment of patients with chronic myelogenous leukemia (CML), thus highlighting the need for novel therapeutic approaches. Since senescence has been recognized as a physiological barrier against tumorigenesis, senescence-based therapy could repr...
Published in Bioorganic & Medicinal Chemistry in Jun 23, 2014
Synthesis of the bis-4-hydroxycoumarin-type compound, 3,3'-[3-(2-hydroxyphenyl)-3-oxopropane-1,1-diyl]bis(4-hydroxy-2H-chromen-2-one), was performed by two alternative pathways, either involving a basic organocatalyzed 1,4-conjugate addition tandem reaction of 4-hydroxycoumarin on chromone-3-carboxylic acid, or a double condensation of 4-hydroxycou...
Published in PLoS ONE in May 07, 2014
Chemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compounds, when tested at sub-toxic doses, induced the lu...
Published in Molecular Carcinogenesis in May 04, 2014
Molecules targeting pro-inflammatory pathways have demonstrated beneficial effects in cancer treatment. More recently, combination of natural and synthetic anti-inflammatory drugs was suggested as an appealing strategy to inhibit tumor growth. Herein, we show that curcumin, a polyphenol from Curcuma longa and celecoxib induce apoptosis in hematopoi...
Published in Food and Chemical Toxicology in Feb 24, 2014
Natural polysulfanes including diallyltrisulfide (DATS) and diallyltetrasulfide (DATTS) from garlic possess antimicrobial, chemopreventive and anticancer properties. However these compounds exhibit chemical instability and reduced solubility, which prevents their potential clinical applicability. We synthetized six DATS and DATTS derivatives, based...
Published in Cancer Letters in Feb 24, 2014
Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate cellular processes by modifying the acetylation status of many proteins. Pathologically altered HDAC activity contributes to cancer development and thus characterization of novel acetylation modulators is important for future anti-cancer therapies. In this study, we identif...
Published in Journal of Medicinal Chemistry in Feb 13, 2014
DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of mye...
Published in Journal of Natural Products in Jan 24, 2014
A chemical investigation of the endophytic fungus Epicoccum nigrum isolated from leaves of Mentha suaveolens collected in Morocco resulted in the isolation of five new polyketides, epicocconigrones A and B (1 and 2), 3-methoxyepicoccone B (3), 3-methoxyepicoccone (4), and 2,3,4-trihydroxy-6-(methoxymethyl)-5-methylbenzaldehyde (5), together with fi...
Published in The Journal of Organic Chemistry in Dec 20, 2013
Four tetrahydroxanthone dimers (1-4) and four biogenetically related monomers (5-8), including the new derivatives (4-6), were isolated from the endophyte Phomopsis longicolla. The absolute configurations of 2-4 were established for the first time by TDDFT ECD calculations and that of phomoxanthone A (1) was revised by X-ray crystallography. Phomox...
Published in Molecular Carcinogenesis in Nov 30, 2013
Our aim was to better understand peroxisome proliferator-activated receptor gamma (PPARγ)-independent pathways involved in anti-cancer effects of thiazolidinediones (TZDs). We focused on Δ2-troglitazone (Δ2-TGZ), a PPARγ inactive TZD that affects breast cancer cell viability. Appearance of TUNEL positive cells, changes in mitochondrial membrane...
Published in Biochemical Pharmacology in Nov 24, 2013
Since centuries, natural compounds from plants, animals and microorganisms were used in medicinal traditions to treat various diseases without a solid scientific basis. Recent studies have shown that plants that were used or are still used in the medieval European medicine are able to provide relieve for many diseases including cancer. Here we summ...