The Consortium Group of the University of Illinois at Chicago (UIC), Research Triangle Institute (RTI) and Glaxo Group Research Ltd. (Glaxo) have combined their vast experience in the isolation and structure elucidation of biologically active natural products to develop a consolidated, integrated program for the isolation of novel, selective anticancer agents which will have the potential for development as cancer chemotherapeutic agents. Plant materials for analysis (500 per year) will be collected by established botanists located primarily in tropical countries, either on the basis of their endemic nature, their local use for treating cancer, parasitic or infectious diseases, or based on a process, using the NAPRALERT database at UIC, of ranking plants previously shown experimentally to have some form of anticancer activity and for which the active principle is not known. Plants acquired as a result of this novel collection strategy will be extracted either at UIC or at RTI, using identical techniques, to afford two fractions which will be evaluated in a battery of 25 assays based on a diverse approach of cytotoxicity, mechanism-based and tumor growth related assays currently established and operational at UIC, RTI and Glaxo. Data from these assays will be stored and analyzed in detail so that a priority list of plants for recollection and fractionation can be formulated by an evaluation panel. This group will have full access to complete computerized literature surveys of the plants in question so that dereplication for known active compounds can be as meaningful as possible. Bioassay-directed fractionation procedures will be employed (at UIC, RTI and Glaxo) for the procurement of pure active principles, which will be structurally characterized. Novel, active compounds thus discovered will be further evaluated in our battery of bioassays. Based on these data and the structure of the isolate, a decision will be made regarding further development of the agent for potential use as a chemotherapeutic agent. These more advanced stages of biological and toxicological testing, as well as synthesis or isolation of larger quantities of lead compounds will be sponsored by Glaxo. The Consortium welcomes the involvement of NCI staff throughout the discovery process, and plans to hold regular meetings of the key scientific personnel at all three sites in order to enhance ongoing communication, exchanges of information and decision-making processes. Excellent facilities for isolation, structure determination, chemical modification, synthesis and in vitro and in vivo biological evaluation are available at the consortial sites for the conduct of this work.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA052956-05
Application #
2095118
Study Section
Special Emphasis Panel (SRC (50))
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Li, Jie; Pan, Li; Deng, Ye et al. (2013) Sphenostylisins A-K: bioactive modified isoflavonoid constituents of the root bark of Sphenostylis marginata ssp. erecta. J Org Chem 78:10166-77
Ren, Yulin; Acuña, Ulyana Muñoz; Jiménez, Francisco et al. (2012) Cytotoxic and NF-?B inhibitory sesquiterpene lactones from Piptocoma rufescens. Tetrahedron 68:2671-2678
Kinghorn, A Douglas; Pan, Li; Fletcher, Joshua N et al. (2011) The relevance of higher plants in lead compound discovery programs. J Nat Prod 74:1539-55
Deng, Ye; Chin, Young-Won; Chai, Hee-Byung et al. (2011) Phytochemical and Bioactivity Studies on Constituents of the Leaves of Vitex Quinata. Phytochem Lett 4:213-217
Ren, Yulin; Kardono, Leonardus B S; Riswan, Soedarsono et al. (2010) Cytotoxic and NF-kappaB inhibitory constituents of Artocarpus rigida. J Nat Prod 73:949-55
Lucas, David M; Edwards, Ryan B; Lozanski, Gerard et al. (2009) The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo. Blood 113:4656-66
Balunas, Marcy J; Jones, William P; Chin, Young-Won et al. (2006) Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project. Chem Biodivers 3:897-915
Balunas, Marcy J; Kinghorn, A Douglas (2005) Drug discovery from medicinal plants. Life Sci 78:431-41
Fang, Liqiong; Chai, Hee-Byung; Castillo, Juan J et al. (2003) Cytotoxic constituents of Brachistus stramoniifolius. Phytother Res 17:520-3
Silva, G L; Cui, B; Chavez, D et al. (2001) Modulation of the multidrug-resistance phenotype by new tropane alkaloid aromatic esters from Erythroxylum pervillei. J Nat Prod 64:1514-20

Showing the most recent 10 out of 30 publications