The overarching goal of this Program Project proposal is to discover naturally products from diverse natural sources that can serve as anticancer drug leads. Project 2, located at the College of Pharmacy, University of Illinois at Chicago (UIC), is comprised of botanical, chemical and biological elements. The primary goals for Project 2 are the discovery of new lead anticancer compound candidates from cyanobacteria and providing tropical plant material for Project 1, housed at The Ohio State University (OSU). The underlying hypothesis for Project 2 is that the diverse natural product structures from cultured non-marine cyanobacteria and tropical plants will be a rich source for anticancer leads. To achieve the stated goals the specific aims for Project 2 are as follows: 1) to obtain, culture, extract, and prepare fractions of cyanobacterial strains. We will obtain 100 non-marine cyanobacterial strains per year. The strain collection will focus on samples collected in the continental U.S. Each strain will be cultured, extracted and prefractionated. The resulting fractions (-700 fractions/year) will be submitted for biological evaluation in the biological test systems available at Core A, Projects 1 and 3 as well as our pharmaceutical partner, Eisai. 2) to isolate and determine the structures of the active cyanobacterial metabolites. Fractions showing promising activity in the biological test systems will be analyzed by LC-MS-NMR to identify any known active compounds (dereplication). Active fractions expected to contain novel metabolites will be fractionated using assay guided fractionation to obtain pure natural product(s). Isolates will be structurally defined using microscale NMR and MS methodologies. Structurally-characterized compounds will be submitted for extensive evaluation in the biological test systems available in Core A, Projects 1 and 3 as well as our pharmaceutical partner, Eisai Research institute. In addition. Core B will perform chemical optimization and modifications of prioritized compounds. We will re-isolate larger amounts of any candidate compounds for further evaluation. 3) To acquire all plant materials that will be required by the proposed Program Project We will provide 300 fully documented plant samples per year to Project 1 for extraction and biologica evaluation. We will also re-collect plant materials for larger scale isolation, as needed.

Public Health Relevance

; The primary purpose of Project 2 of this program project is to discover new cancer chemotherapeutic leads from cyanobacteria and to supply plants from tropical rainforests for further investigation in Project 1. The proposed research will impact human health by creating new lead compounds for the development of drugs to treat cancer. Some of the compounds discovered may work by new mechanism of action, thus increasing our understanding how to treat this disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Ohio State University
United States
Zip Code
Sica, Vincent P; Rees, Evan R; Raja, Huzefa A et al. (2017) In situ mass spectrometry monitoring of fungal cultures led to the identification of four peptaibols with a rare threonine residue. Phytochemistry 143:45-53
Henkin, Joshua M; Sydara, Kongmany; Xayvue, Mouachanh et al. (2017) Revisiting the linkage between ethnomedical use and development of new medicines: A novel plant collection strategy towards the discovery of anticancer agents. Journal of medicinal plant research 11:621-634
Paguigan, Noemi D; Al-Huniti, Mohammed H; Raja, Huzefa A et al. (2017) Chemoselective fluorination and chemoinformatic analysis of griseofulvin: Natural vs fluorinated fungal metabolites. Bioorg Med Chem 25:5238-5246
Wang, Jiang; Zhu, Xiaohua; Kolli, Shamala et al. (2017) Plasma pharmacokinetics and bioavailability of verticillin A following different routes of administration in mice using liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 139:187-192
Chen, Wei-Lun; Ren, Yulin; Ren, Jinhong et al. (2017) (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks. J Nat Prod 80:659-669
Paguigan, Noemi D; El-Elimat, Tamam; Kao, Diana et al. (2017) Enhanced dereplication of fungal cultures via use of mass defect filtering. J Antibiot (Tokyo) 70:553-561
Ren, Yulin; Chen, Wei-Lun; Lantvit, Daniel D et al. (2017) Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity. J Nat Prod 80:648-658
Acuña, Ulyana Munoz; Curley Jr, Robert W; Fatima, Nighat et al. (2017) Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells. Anticancer Res 37:1617-1623
Ren, Yulin; Gallucci, Judith C; Kinghorn, A Douglas (2017) An Intramolecular CAr-H•••O=C Hydrogen Bond and the Configuration of Rotenoids. Planta Med 83:1194-1199
Brooks, Wilson C; Paguigan, Noemi D; Raja, Huzefa A et al. (2017) qNMR for profiling the production of fungal secondary metabolites. Magn Reson Chem 55:670-676

Showing the most recent 10 out of 126 publications