340 A CADD Approach to Non-Toxic Enediyne Anti-Tumor Drugs

Thursday, November 5, 2009: 2:00 PM
Santa Fe (Camino Real Hotel)
Elfi Kraka , Chemistry, Southern Methodist University, Dallas, TX
Dieter Cremer , Chemistry, Southern Methodist University, Dallas, TX
Tell Tuttle , Department of Chemistry, University of Strathclyde, Glasgow, Scotland
An expert use of computer assisted drug design (CADD) can lead to a substantial reduction of cost and time for the development of a new drug. CADD can be made more powerful by an educated use of quantum chemical methods. This is discussed in connection with the design of new nontoxic anticancer leads utilizing the enediyne-principle. This principle was developed by nature in billions of years. It is based on the ability of naturally occurring enediynes to destroy the DNA of toxic bacteria and viruses. Attempts to use the enediyne-principle as a basis for an anticancer drug have failed because the naturally occurring enediynes cannot differentiate between tumor and normal cells and, therefore, they are highly toxic. Using CADD we first investigated the biological activity of naturally occurring enediynes and then introduced modifications of the enediyne 'warhead' with the objective of making it target-specific. This work has led to a new rational design concept for non-toxic enediyne anticancer leads, which will be presented.