Molecular orbital analysis and quantitative structure-activity relationships for the anthracycline antibiotics.

Semiempirical CNDO/2 calculations of the electronic and molecular structures have been carried out for six antitumor anthracycline antibiotics. The strong correlation between their biological activity and such molecular properties as chromophore dipole moment, energy of frontier orbitals, and steric volumes was found and the proper QSAR equations were constructed. The molecular mechanics model showed the weak dependence the DNA-intercalation energy on differences in chromophore constituents (C4 and C9 positions). The expression for the intercalation energy has also been obtained on the ground of a quantum-statistical approach; it was applied to the DNA-intercalation energy calculations for the same six anthracyclines. The results agree with the molecular mechanics ones quite satisfactory.