MOLECULAR MODELING OF TUMOR-PROMOTING AND NONPROMOTING DITERPENE ESTERS AND MOLECULAR COORDINATES OF THE POTENT IRRITANT RESINIFERATOXIN

The lowest energy conformer of seventeen diterpenes, representing five different phorbol and daphnane diterpene nuclei, has been generated. TPA possessed the highest minimum free energy of these compounds; all other compounds possessed a lower minimum free energy. Compounds based on the resiniferonol nucleus possessed the lowest minimum free energy (9.4-16.6% of that of TPA). The molecular co-ordinates of the non-pro moting but potent irritant resiniferatoxin (Rx) are also reported. The se studies may be important in elucidation of the biochemical mechanis ms of action of diterpene esters, including an understanding of the in teractions of diterpene esters with the phorbol ester binding domain o f the protein kinase C isoform family.