Docking and Molecular Dynamics Studies on DNA-Heterocyclic Enediynes Interaction to Identify the Preferred Binding Mode

Enediyne antibiotics are a class of potent DNA-cleaving antitumor agents. Searching for promising analogs of enediyne antibiotics, the features of interaction with the DNA of enediynes fused with heterocycles have been studied using molecular modeling methods. Depending on their structure, 10-membered heteroenediynes can exhibit both intercalator properties and bind to the minor groove of DNA. Variation of the heterocyclic part annulated with the enediyne cycle as well as the attachment of substituents at the enediyne core makes it possible to change the DNA method of binding mode, from intercalation to minor groove-binding.