The major objectives of this work is to isolate, purify and determine the structure of the anticancer compounds present in Catharanthus roseus, Catharanthus trichophyllus, Rhazya stricta, and Gnidia kraussiana. Although Catharanthus roseus is a well established source of antitumor agents of the dimeric indole alkaloid class, several highly active fractions remain to be studied for their active constituents. The crude alkaloid mixtures will be separated initially by pH gradient techniques and subsequently by column chroamtography; monitoring each step with an appropriate biological assay technique. A number of active bisindole alkaloids have been isolated and must be characterized. Isolated compounds will be identified by their mp, mass, UV and IR spectra, optical rotation CD and PMR and CMR spectra. Structure elucidation will be carried out by interpretation of these data, chemical correlation with known compounds and in particularly difficult cases by single crystal X-ray crystallography. The alkaloid fraction of the closely related plant Catharanthus trichophyllus also displays very good in vivo antitumor activity and it is proposed to isolate additional in vivo active compounds from this fraction by techniques similar to those described above for Catharanthus roseus. The Asian plant Rhazya stricta has afforded some in vitro active compounds but further isolation studies are needed on active fractions and some structural studies are still required. Rhazya orientalis will be grown for biological testing. Gnidia kraussiana has afforded a number of exceptionally cytotoxic fractions which have been obtained and it is proposed to isolate the compounds responsible for this activity. These are suspected to be tigliane or daphnane esters.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA020164-11
Application #
3165254
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1979-04-01
Project End
1989-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Pharmacy
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Pengsuparp, T; Kingston, D G; Neidigh, K A et al. (1996) Evaluation of the cytotoxic mechanism mediated by baccatin III, the synthetic precursor of taxol. Chem Biol Interact 101:103-14
Oksuz, S; Gurek, F; Lin, L Z et al. (1996) Aleppicatines A and B from Euphorbia aleppica. Phytochemistry 42:473-8
Pengsuparp, T; Cai, L; Constant, H et al. (1995) Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1 reverse transcriptase. J Nat Prod 58:1024-31
Sun, H D; Lin, Z W; Niu, F D et al. (1995) Cytotoxic ent-kaurene diterpenoids from three Isodon species. Phytochemistry 38:437-42
Gil, R R; Lin, L Z; Chai, H B et al. (1995) Cardenolides from Nierembergia aristata. J Nat Prod 58:848-56
Oksuz, S; Gurek, F; Gil, R R et al. (1995) Four diterpene esters from Euphorbia myrsinites. Phytochemistry 38:1457-62
Wang, J N; Hou, C Y; Liu, Y L et al. (1994) Swertifrancheside, an HIV-reverse transcriptase inhibitor and the first flavone-xanthone dimer, from Swertia franchetiana. J Nat Prod 57:211-7
Likhitwitayawuid, K; Angerhofer, C K; Chai, H et al. (1993) Cytotoxic and antimalarial alkaloids from the tubers of Stephania pierrei. J Nat Prod 56:1468-78
Saifah, E; Puripattanavong, J; Likhitwitayawuid, K et al. (1993) Bisamides from Aglaia species: structure analysis and potential to reverse drug resistance with cultured cells. J Nat Prod 56:473-7
Somanabandhu, A; Nitayangkura, S; Mahidol, C et al. (1993) 1H- and 13C-nmr assignments of phyllanthin and hypophyllanthin: lignans that enhance cytotoxic responses with cultured multidrug-resistant cells. J Nat Prod 56:233-9

Showing the most recent 10 out of 38 publications