Abstract

This research project is designed to carry out bioassay-directed isolation, structural elucidation, and chemical studies of novel antineoplastic agents from higher plants which have confirmed activity in a panel of human tumors in cell culture. The cell lines which are in place (HT-29, A549, MCF-7, RPMI-7951 and TE671) have been chosen based on consideration of refractory disease-type and overlap with the panel of human tumor cell lines being established by the National Cancer Institute (NCI). Plant materials are obtained through botanical contacts world-wide and from NCI. A large number of plant extracts are on hand with confirmed activity in these systems and/or 9PS. Bioactivity- directed fractionation is underway on Annona species, Canaga oderata, Anomodon species and other mosses including Claopodium crispifolium and polytrichum ohioensis. Structural work and chemical studies are underway on crystalline actives from psorospermum febrifugum, Annona densicoma, A. reticulata, polytrichum ohioensis and others, Compounds with selective activity for the human tumor cells have been discovered and are under study. Selected novel actives will be submitted to the NCI for further evaluation in the NCI human tumor panel and animal models. This research will provide additional novel antineoplastic agents which have clinical potential. Compounds discovered will also serve as structural prototypes for analog synthesis and as biochemical probes which may aid in the elucidation of novel mechanisms of growth control and novel therapeutic targets.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA033326-07
Application #
3171250
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1982-09-30
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Schools of Pharmacy
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Soonthornchareonnon, N; Suwanborirux, K; Bavovada, R et al. (1999) New cytotoxic 1-azaanthraquinones and 3-aminonaphthoquinone from the stem bark of Goniothalamus marcanii. J Nat Prod 62:1390-4
Permana, P A; Ho, D K; Cassady, J M et al. (1994) Mechanism of action of the antileukemic xanthone psorospermin: DNA strand breaks, abasic sites, and protein-DNA cross-links. Cancer Res 54:3191-5
Zheng, G Q; Ho, D K; Elder, P J et al. (1994) Ohioensins and pallidisetins: novel cytotoxic agents from the moss Polytrichum pallidisetum. J Nat Prod 57:32-41
Zennie, T M; Cassady, J M (1990) Funebradiol, a new pyrrole lactone alkaloid from Quararibea funebris flowers. J Nat Prod 53:1611-4
Cassady, J M; Baird, W M; Chang, C J (1990) Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents. J Nat Prod 53:23-41
Habib, A M; Reddy, K S; McCloud, T G et al. (1987) New xanthones from Psorospermum febrifugum. J Nat Prod 50:141-5
Sun, N J; Antoun, M; Chang, C J et al. (1987) New cytotoxic aristolactams from Pararistolochia flos-avis. J Nat Prod 50:843-6
Suwanborirux, K; Chang, C J; Cassady, J M (1987) Novel chromones from Spathelia sorbifolia. J Nat Prod 50:102-7
McCloud, T G; Smith, D L; Chang, C J et al. (1987) Annonacin, a novel, biologically active polyketide from Annona densicoma. Experientia 43:947-9
Pachuta, R R; Cooks, R G; Cassady, J M et al. (1986) Antineoplastic agents from higher plants: application of tandem mass spectrometry to xanthones from Psorospermum febrifugum. J Nat Prod 49:412-23

Showing the most recent 10 out of 11 publications