In this Program Project renewal application, the applicant group is representative of three primary institutions, The Ohio State University (OSU), the University of Illinois at Chicago (UIC), and the University of North Carolina at Greensboro (UNCG). The participants have combined their vast experience in the isolation, structure elucidation, and biological evaluation of natural products, to the development of a consolidated, integrated program for the discovery of novel anticancer agents of diverse origin for development as cancer chemotherapeutic agents. Plant materials to be studied in Project 1 (OSU) will be collected by established botanists located in tropical countries with the assistance of the NAPRALERT database (Project 2; UIC), and lichens and their fungal associates (Project 1), cyanobacteria (Project 2) and filamentous fungi (Project 3; UNCG) will also be accessed. Organisms acquired will be extracted and evaluated in a diverse battery of relevant mechanism-based, cell-based, and tumor-growth related assays currently operational at OSU (Project 1), UIC (Core 1), Columbia University (through Project 3), and via other external collaborators (through Core A at OSU). Dereplication of known active compounds will be accomplished at OSU, UIC, and UNCG using computerized literature surveys and LC-MS coupled to bioassays. Bioassay-directed fractionation will be employed in Projects 1-3 for the elucidation of the active principles. Lead development of active natural products via medicinal chemistry and pharmacokinetics-related studies will be conducted at OSU (Core 2), facilitated by the OSU Biostatistics group (Core A). Novel, active compounds thus discovered will be further evaluated in our panel of in vitro and in vivo bioassays (Projects 1 and 3, Core A, and some external collaborators). Group decisions will be made regarding the further development of agents for potential use as anticancer agents. The more advanced stages of biological and toxicological testing will be aided through consultation with the Drug Discovery Institute of the OSU Comprehensive Cancer Center (through Core A). The Consortium will work with the involvement of the NCI Program Official in the discovery process, and plans to hold regular meetings of key scientific personnel (inclusive of our External and OSU Internal Scientific Advisory Boards) to enhance communication and decision- making processes, to be organized by Core A. Excellent facilities for the isolation, structure determination, chemical modification, synthesis, and in vitro and in vivo biological evaluation, and overall project data management are available. The overarching goal of this P01 is to identify lead compounds that ultimately have therapeutic value for the treatment of cancer.
Cancer is responsible for about one in every four deaths in the United States, and new treatments are urgently needed. It is the overall goal of the integrated studies in this renewal application to discover novel chemicals from selected tropical rainforest plants, as well as lichens, cyanobacteria and fungi, for development as cancer chemotherapeutic agents, particularly for tumors not cured by current treatment methods.
|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|
|Crnkovic, Camila M; Krunic, Aleksej; May, Daniel S et al. (2018) Calothrixamides A and B from the Cultured Cyanobacterium Calothrix sp. UIC 10520. J Nat Prod 81:2083-2090|
|Wilson, Tyler A; Tokarski 2nd, Robert J; Sullivan, Peter et al. (2018) Total Synthesis of Scytonemide A Employing Weinreb AM Solid-Phase Resin. J Nat Prod 81:534-542|
|Lu, Chunwan; Yang, Dafeng; Sabbatini, Maria E et al. (2018) Contrasting roles of H3K4me3 and H3K9me3 in regulation of apoptosis and gemcitabine resistance in human pancreatic cancer cells. BMC Cancer 18:149|
|El-Elimat, Tamam; Rivera-Chávez, José; Burdette, Joanna E et al. (2018) Cytotoxic homoisoflavonoids from the bulbs of Bellevalia flexuosa. Fitoterapia 127:201-206|
|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|
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