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Bioactive Constituents of Aronia melanocarpa and Sphenostylis marginata ssp. erecta

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2014, Doctor of Philosophy, Ohio State University, Pharmacy.
Natural products have played an important role for many decades in drug discovery to combat cancer. As part of a collaborative, multi-disciplinary approach to the discovery of new naturally occurring cancer chemopreventive or chemotherapeutic agents, two edible plants, namely, Aronia melanocarpa (black chokeberry) and Sphenostylis marginata ssp. erecta (African yellow pea), showed activity in initial hydroxyl radical-scavenging and quinone reductase-induciton screening assays, and thus were selected for further phytochemical and biological investigation. Bioassay-guided fractionation of the ethyl acetate-soluble extract of A. melanocarpa fruits, using hydroxyl radical-scavenging and quinone reductase-induciton assays, led to the isolation of a new depside (81) and two known depsides (82 and 83), along with an additional twenty-one known compounds (64-66, 70, and 84-100). Among the known compounds obtained, eighteen compounds (81-87, 89, 90, and 92-100) were isolated from A. melanocarpa for the first time. The new compound 81 and the known compounds 82 and 83 represent a novel class of depsides that has been reported only relatively recently. In the present study, the four-bond HMBC correlations of 81-83 were obtained to provide direct evidence for fully unambiguous NMR assignments of these three compounds. Among all the twenty-four compounds isolated, seventeen compounds showed significant hydroxyl radical-scavenging activity, with hyperin (64, ED50 0.17 uM) being of the greatest potency. The new compound 81 also exhibited potent antioxidant activity (ED50 0.44 uM) in this assay. The quinone reductase-induction assay showed that protocatechuic acid (84, CD 4.3 uM), neochlorogenic acid methyl ester (96, CD 6.7 uM), and quercetin (99, CD 3.1 uM) doubled quinone reductase activity at concentrations less than 10 uM. The chloroform-soluble extract of the root bark of S. marginata ssp. erecta was also fractionated under the guidance of both hydroxyl radical-scavenging and quinone reductase-induciton assays, and resulted in the isolation of sphenostylisins A-C (107-109), three complex dimeric compounds representing two novel carbon skeletons, as well as an additional eight new compounds, sphenostylisins D-K (110-117). All these new compounds obtained were evaluated against a panel of in vitro bioassays. Of these isolates, eight compounds (107-110 and 114-117) exhibited potent hydroxyl radical-scavenging activity (ED50 values range from 0.60 to 2.6 uM). Six compounds (107-110, 114, and 115) showed quinone reductase-inducing activity, with sphenostylisin C (109, CD 2.1 uM) being the most potent. Eight compounds (107-114) showed NF-kB p65 inhibitory activity. In particular, sphenostylisin A (107), representing a novel carbon skeleton, was found to be a very potent NF-kB p65 inhibitor with an IC50 value of 6 nM. This compound (107) also showed cytotoxicity (IC50 1.6 uM) against the HT-29 cell line. Based on the structural features and similarities of these eleven new compounds (107-117), a plausible biogenetic pathway and a preliminary structure-activity relationship among them were discussed in the present study. In summary, considering the high abundance and potent activities of bioactive constituents present in A. melanocarpa and S. marginata ssp. erecta, these two plants can be regarded as excellent sources of lead compounds for the development of drugs to combat cancer.
A. Douglas Kinghorn (Advisor)
287 p.

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Citations

  • Li, J. (2014). Bioactive Constituents of Aronia melanocarpa and Sphenostylis marginata ssp. erecta [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1387764682

    APA Style (7th edition)

  • Li, Jie. Bioactive Constituents of Aronia melanocarpa and Sphenostylis marginata ssp. erecta. 2014. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1387764682.

    MLA Style (8th edition)

  • Li, Jie. "Bioactive Constituents of Aronia melanocarpa and Sphenostylis marginata ssp. erecta." Doctoral dissertation, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1387764682

    Chicago Manual of Style (17th edition)