The overall goal of this program proposal is to discover naturally occurring anticancer lead compounds that will be more effective than currently available cancer chemotherapeutic agents. Project 2, at the College of Pharmacy, UIC is comprised of botanical, chemical and biological elements.
The specific aims for Project 2 are as follows: 1) To obtain, culture, and prepare extracts of cyanobacterial strains. We will obtain, culture, and extract 100 cyanobacterial strains a year. Each strain will be cultured in two different media, producing 200 cyanobacterial samples for biological evaluation in Projects 1 (OSU), 3 (RTI)and Cores A (UIC) and C (B-MS). 2) To isolate and determine the structures of the active cyanobacterial metabolites. Extracts showing antineoplastic activity will be fractionated using bioguided fractionation protocols to obtain pure natural product(s). We will use microcoil NMR and LC-MS methods to determine the structures of the pure active compounds;these sensitive analytical techniques reduce the amount of pure material needed for structure elucidation to 10-50ug and thus speed up the isolation and structure determination process. Structurally characterized active isolates will be submitted for more extensive evaluation in biological test systems available at Cores A and C and Projects 1 and 3 as well as chemical optimization (Core B). We will re-isolate larger amounts of any promising candidate compounds for further evaluation. 3) To acquire all plant materials that will be required by the proposed Program Project, inclusive of 300 new and fully documented plant samples for extraction and initial biological evaluation per year, as well as re-collected plant materials for larger scale isolation leading to more detailed biological evaluation as needed. In addition, the UIC project will provide analytical support for Projects 1 (OSU)and 3 (RTI)in the structure determination of minor active metabolites using microcoil NMR.This will enable all projects to perform structure determination on 10-50 ug of active isolates. Relevance of Research to Public Health The primary purposes of this part of the program project are to discover new cancer chemotherapeutic agents from cyanobacteria and to supply plants from tropical rainforests for investigation. This will be done in a coordinated manner with the other technical and administrative components of this project.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Ohio State University
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Ren, Yulin; Anaya-Eugenio, Gerardo D; Czarnecki, Austin A et al. (2018) Cytotoxic and NF-?B and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives. Bioorg Med Chem 26:4452-4460
Crnkovic, Camila M; May, Daniel S; Orjala, Jimmy (2018) The impact of culture conditions on growth and metabolomic profiles of freshwater cyanobacteria. J Appl Phycol 30:375-384
Woodard, John L; Huntsman, Andrew C; Patel, Pratiq A et al. (2018) Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones. Bioorg Med Chem 26:2354-2364
Ren, Yulin; Gallucci, Judith C; Li, Xinxin et al. (2018) Crystal Structures and Human Leukemia Cell Apoptosis Inducible Activities of Parthenolide Analogues Isolated from Piptocoma rufescens. J Nat Prod 81:554-561
May, Daniel S; Kang, Hahk-Soo; Santarsiero, Bernard D et al. (2018) Ribocyclophanes A-E, Glycosylated Cyclophanes with Antiproliferative Activity from Two Cultured Terrestrial Cyanobacteria. J Nat Prod 81:572-578
Oblinger, Janet L; Burns, Sarah S; Huang, Jie et al. (2018) Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation. Exp Neurol 299:299-307
Amrine, Chiraz Soumia M; Raja, Huzefa A; Darveaux, Blaise A et al. (2018) Media studies to enhance the production of verticillins facilitated by in situ chemical analysis. J Ind Microbiol Biotechnol 45:1053-1065
Young, Alexandria N; Herrera, Denisse; Huntsman, Andrew C et al. (2018) Phyllanthusmin Derivatives Induce Apoptosis and Reduce Tumor Burden in High-Grade Serous Ovarian Cancer by Late-Stage Autophagy Inhibition. Mol Cancer Ther 17:2123-2135
Acuña, Ulyana Muñoz; Mo, Shunyan; Zi, Jiachen et al. (2018) Hapalindole H Induces Apoptosis as an Inhibitor of NF-?B and Affects the Intrinsic Mitochondrial Pathway in PC-3 Androgen-insensitive Prostate Cancer Cells. Anticancer Res 38:3299-3307
Al-Huniti, Mohammed H; Rivera-Chávez, José; Colón, Katsuya L et al. (2018) Development and Utilization of a Palladium-Catalyzed Dehydration of Primary Amides To Form Nitriles. Org Lett 20:6046-6050

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