The goal of this proposal is to rationally design novel cancer chemotherapeutic agents based on the pharmacophore of bryostatin 1. This will be accomplished using a three part system of molecular modeling, chemical synthesis, and biological assays. Programming the pharmacophore of bryostatin 1 into a modeling program will allow use of that program to find a best fit between the pharmacophore model and the proposed drug candidates. Simplified analogues or novel structures that keep the key functionally of the actual drugs intact will be designed and chemically synthesized. Upon synthesis of these compounds, the biological assays that have been used previously for the bryostatins will be used to test the effectiveness of the new drugs. The system can be fine tuned because the synthetic route is simple and flexible, allowing for small conformational changes in the pharmacophore. Those compounds that are efficiently synthesized and contain biological activity equivalent to or greater than bryostatin 1 will be excellent candidates to be tested for cancer therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA077899-01
Application #
2639686
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lohrey, Nancy
Project Start
1998-10-19
Project End
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305