Doxorubicin and Related Compounds. I. Physicochemical Characterization of the DNA Complex

The study of molecular interactions between drugs and biological macromolecules in solution has received considerable attention in recent years. Researchers in this field of biophysical chemistry, although well aware of the different situation present in in vivo systems (those that show a complexity of molecular structures in a dynamic state and in a polyphasic system as that represented by living cells), believe that information obtained at the molecular level is a prerequisite for the complete understanding of the mechanism of action of drugs. From the standpoint of the medicinal chemist, any molecular property related to biological activity is of great interest; a knowledge of structural requirements that exhibit a given property allows an understanding of the chemical modifications needed to optimize desired pharmacological behavior within a given class of related compounds. This is particularly important in the case of the antitumor anthracyclines. Even though hundreds of new compounds have been made available for biological evaluation and a variety of pharmacological properties of the parent compounds have been investigated in different laboratories, programs aimed at the development of new analogs are still based solely on empirical considerations that have been derived from results obtained in standard biological screening systems.