A role for dipole moment in the activity of cyclolignans

The reactivity of podophyllotoxin and several related cyclolignans with different aminoderivatives has been checked with the aim of achieving a better understanding of their physico-chemical properties and of relating them to their pharmacological behaviour. Molecular modelling studies have shown that the relative orientation of the dipole moment in these cyclolignans might be directing the attack of these nucleophiles in the biosubstrate to different positions. These results also provide insights into the structure-activity relationships and further support for the recently proposed biological mechanism of cyclolignans. (C) 2000 Elsevier Science B.V. All rights reserved.