Project 1 at The Ohio State University (OSU) is comprised of isolation chemistry, dereplication, and biological tesfing components.
Specific Aims 1 -4 will involve: (a) preparing extracts of all primary plant materials provided mainly from Project 2 (University of Illinois at Chicago, UIC) for inifial biological screening;(b) LC-MS dereplication studies on active leads following preliminary screening (in order to prioritize samples for activity-guided fractionation);(c) purification procedures using chromatographic methods (guided by both in-house bioassays and those elsewhere, in the program project);and (d) compound structure elucidafion, respectively. The structures of bioactive compounds will be determined using modern spectroscopic methods, backed up by chemical transformations and X-ray crystallography [work to be performed Projects 1, 2, and the medicinal chemistry portion of Core B (OSU)], where necessary.
In Specific Aim 5, plant extracts will be subjected to primary screenirig against a small panel of cancer cells at Core A (UIC). Extracts of interest will then be submitted for testing in Project 1 (OSU), Project 3 [Columbia University via the University of North Carolina at Greensboro (UNCG)], and a new pharmaceufical partner, Eisai Inc., Andover, MA (through Core C at OSU)}: The Project 1 bioassays will involve testing against the OSU-CLL (chronic lymphocytic leukemia) and OSU-NB (normal B-cell) cell lines, and against primary tumor samples from CLL pafients at the OSU James Cancer Hospital. Testing will also occur with three in-house mechanisfic assays [viz., nuclear factor-KB (NF-KB), mitochondrial transmembrane potenfial (MTP) inhibifion, and Semaphorin-3]. Acfive compounds from Project 1 will also be tested in the in vitro biological test systems available at UIC (Core A), Columbia University (Project 3), and Eisai Inc. (through Core C), with promising compounds also evaluated in in vivo assays in Cores A and C. Collaborative in vitro and testing on promising lead compounds from Project 1 will be performed with colleagues at The Oho State University Wexner Medical Center (OSUWMC).
In Specific Aim 6, scale-up isolations when required by programmatic needs, with compound scale up also conducted by synthesis in collaboration with Core B. Stringent efforts will be made to progress new bioactive compounds towards preclinical evaluafion as potential anficancer compounds.

Public Health Relevance

The primary purpose of this part of the program project is to discover new cancer chemotherapeutic agents from plants, that will be collected from tropical rainforests. In order to do this, our group will perform chemical and biological studies in a coordinated manner with the other components of this project.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA125066-06A1
Application #
8608727
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (O1))
Project Start
2006-12-01
Project End
2019-04-30
Budget Start
2014-06-06
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$260,433
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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