Browsing by Author "Dai, Yumin"

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    Isolation, Synthesis and Structure-Activity Relationship Study of Anticancer and Antimalarial Agents from Natural Products
    Dai, Yumin (Virginia Tech, 2013-11-18)
    The Kingston group's engagement in an International Cooperative Biodiversity Group (ICBG) program and a collaborative research project established between Virginia Tech and the Institute for Hepatitis and Virus Research (IHVR) has focused on the search for bioactive natural products from tropical forests in both Madagascar and South Africa. As a part of this research, a total of four antiproliferative extracts were studied, leading to the isolation of fourteen novel compounds with antiproliferative activity against the A2780 human ovarian cancer line. One extract with antimalarial activity was studied, which led to the isolation of two new natural products with antiplasmodial activity against a drug-resistant Dd2 strain of Plasmodium falciparum. The plants and their secondary metabolites are discussed in the following order: two new antiproliferative acetogenins from a Uvaria sp. (Annonaceae); two new antiproliferative calamenene-type sesquiterpenoids from Sterculia tavia (Malvaceae); two new antiproliferative triterpene saponins from Nematostylis anthophylla (Rubiaceae); six new antiproliferative homoisoflavonoids and two new bufatrienolides from Urginea depressa (Asparagaceae); and two new antiplasmodial anthraquinones from Kniphofia ensifolia (Asphodelaceae). The structures of all these compounds were determined by analysis of their mass spectrometric, 1D and 2D NMR, UV and IR spectroscopic and optical rotation data. Other than structural elucidation, this work also involved bioactivity evaluations of all the isolates, as well as total synthesis of the two antiproliferative sesquiterpenoids, and a structure-activity relationship (SAR) studies on the antiplasmodial anthroquinones.
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    Mechanism of Rifampicin Inactivation in Nocardia farcinica
    Abdelwahab, Heba; Del Campo, Julia S. Martin; Dai, Yumin; Adly, Camelia; El-Sohaimy, Sohby; Sobrado, Pablo (PLOS, 2016-10-05)
    A novel mechanism of rifampicin (Rif) resistance has recently been reported in Nocardia farcinica. This new mechanism involves the activity of rifampicin monooxygenase (RifMO), a flavin-dependent monooxygenase that catalyzes the hydroxylation of Rif, which is the first step in the degradation pathway. Recombinant RifMO was overexpressed and purified for biochemical analysis. Kinetic characterization revealed that Rif binding is necessary for effective FAD reduction. RifMO exhibits only a 3-fold coenzyme preference for NADPH over NADH. RifMO catalyzes the incorporation of a single oxygen atom forming an unstable intermediate that eventually is converted to 2′-N-hydroxy-4-oxo-Rif. Stable C4a-hydroperoxyflavin was not detected by rapid kinetics methods, which is consistent with only 30% of the activated oxygen leading to product formation. These findings represent the first reported detailed biochemical characterization of a flavin-monooxygenase involved in antibiotic resistance.
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    Phytochemicals from Graviola fruit selectively inhibit breast cancer cells growth involving EGFR signaling pathway
    Dai, Yumin (Virginia Tech, 2010-03-30)
    There is a growing interest in using naturally-occurring compounds as cancer chemopreventive or chemotherapeutic agents. This study investigated the anticancer potential of the graviola fruit extract (GFE) on specific human breast cancer (BC) cells. GFE was found in our preliminary screening to selectively inhibit the growth of certain human BC cells (MDA-MB-468) but did not affect non-transformed breast epithelial MCF-10A cells. GFE treatment was very effective against the growth of MDA-MB-468 BC cells with an IC50 of 4.8 µg/ml. In vitro, effects of GFE treatment on MDA-MB-468 BC cells were further examined for apoptosis and cell proliferation. Apoptosis, determined qualitatively and quantitatively, was enhanced and accompanied by caspase-3 activation. GFE treatment also induced cell cycle arrest at the G1 cell cycle phase and significantly reduced the percentage of MDA-MB-468 cells in S-phase following 24h of exposure. Moreover, the results from analysis of the mRNA expression of epidermal growth factor receptor (EGFR), which plays an important role in regulating cell development and death, by qRT-PCR, suggested that GFE-induced selective growth inhibition of MDA-MB-468 BC cells is associated with a significant inhibition of EGFR gene expression in the cells. In vivo, dietary treatment with GFE significantly inhibited MDA-MB-468 tumor growth implanted in mice by reducing tumor wet weight and significantly reduced EGFR and p-ERK protein expression in tumors. Overall, GFE attenuated cell proliferation, induced apoptosis, modulated cell cycle regulation and downregulated EGFR gene expression both in vitro and in vivo. These discoveries support the further studies to fully elucidate the antitumor potential of GFE and its components as a dietary agent for BC.