Abstract

This research project is designed to carry out the isolation and structural elucidation of novel antineoplastic agents from higher plants which have confirmed activity in various cell culture (9ASK, 9KB, 9PS, human lung) and animal tumor models (P388 mouse leukemia). In addition to bioassay-directed fractionation we will employ tandem MS analysis to detect analogs of the significant lead compounds homoharringtonine (Cephalotaxus), psorospermin (Psorospermum) and podolactone C (Podocarpus species). Structural work is underway on pure actives from Cephalotaxus, Psorospermum, and Desfontainia. Fractionation is underway on Annona densicoma, Claopodium crispifolium, Psorospermum febrifugum and others with confirmed antineoplastic activity. A total of about 60 active plants are available for study. Additional leads will be developed through botanical contacts. Novel cell culture systems designed to target tubulin and specific human tumors will be employed. All novel actives will be submitted to the NCI for evaluation in the NCI animal tumor panel. 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 tools which may aid in the elucidation of novel mechanisms of growth control.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA033326-04
Application #
3171249
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1982-09-30
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
4
Fiscal Year
1985
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