The novel dipeptide CC-1065 is a potent antitumor antibiotic which has been shown to be more cytotoxic than maytansine, adriamycin, and actinomycin D against a variety of murine and human cancer cells. Unfortunately, it also shows a lethal delayed hepatotoxicity at therapeutic antineoplastic doses in rodents. Recent work at the Upjohn Company has shown, however, that a highly modified analog of CC-1065 can be quite active while having a much reduced hepatotoxicity. We propose to continue our current studies aimed at completing the synthesis of CC-1065 as well as systematically synthesizing a number of structural analogs of CC-1065. Our versatile photochemical approach will provide a variety of B and C type units, and will provide a new route to the dienone A unit and its analogs. In addition, an in-depth study of appropriate coupling and blocking procedures will be made in order to assemble the tricyclic units. Final objectives in addition to CC-1065 itself include a variety of deoxy analogs, as well as analogs containing sulfur or oxygen in place of the indole nitrogens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA041995-03
Application #
3182662
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Alabama in Tuscaloosa
Department
Type
Schools of Arts and Sciences
DUNS #
City
Tuscaloosa
State
AL
Country
United States
Zip Code
35487