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.
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.
|El-Elimat, Tamam; Raja, Huzefa A; Figueroa, Mario et al. (2015) Sorbicillinoid analogs with cytotoxic and selective anti-Aspergillus activities from Scytalidium album. J Antibiot (Tokyo) 68:191-6|
|Yong, Yeonjoong; Pan, Li; Ren, Yulin et al. (2014) Assay development for the discovery of semaphorin 3B inducing agents from natural product sources. Fitoterapia 98:184-91|
|Ren, Yulin; Yuan, Chunhua; Qian, Yanrong et al. (2014) Constituents of an extract of Cryptocarya rubra housed in a repository with cytotoxic and glucose transport inhibitory effects. J Nat Prod 77:550-6|
|Pan, Li; Woodard, John L; Lucas, David M et al. (2014) Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species. Nat Prod Rep 31:924-39|
|Deng, Youcai; Chu, Jianhong; Ren, Yulin et al. (2014) The natural product phyllanthusmin C enhances IFN-? production by human NK cells through upregulation of TLR-mediated NF-?B signaling. J Immunol 193:2994-3002|
|El-Elimat, Tamam; Raja, Huzefa A; Day, Cynthia S et al. (2014) Greensporones: resorcylic acid lactones from an aquatic Halenospora sp. J Nat Prod 77:2088-98|
|Pérez, Lynette Bueno; Still, Patrick C; Naman, C Benjamin et al. (2014) Investigation of Vietnamese plants for potential anticancer agents. Phytochem Rev 13:727-739|
|Ren, Yulin; Lantvit, Daniel D; Deng, Youcai et al. (2014) Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei. J Nat Prod 77:1494-504|
|Luo, Shangwen; Kang, Hahk-Soo; Krunic, Aleksej et al. (2014) Carbamidocyclophanes F and G with Anti-Mycobacterium tuberculosis Activity from the Cultured Freshwater Cyanobacterium Nostoc sp. Tetrahedron Lett 55:686-689|
|Bueno Pérez, Lynette; Pan, Li; Muñoz Acuña, Ulyana et al. (2014) Caeruleanone A, a rotenoid with a new arrangement of the D-ring from the fruits of Millettia caerulea. Org Lett 16:1462-5|
Showing the most recent 10 out of 65 publications