A role for dipole moment in the activity of cyclolignans

The reactivity of podophyllotoxin and several related cyclolignans with dif ferent 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 th at the relative orientation of the dipole moment in these cyclolignans migh t be directing the attack of these nucleophiles in the biosubstrate to diff erent positions. These results also provide insights into the structure-act ivity relationships and further support for the recently proposed biologica l mechanism of cyclolignans. (C) 2000 Elsevier Science B.V. All rights rese rved.