MDR Reversal by Deprenylated Tetracyclic and Hexacyclic Analogues of N-Acetylardeemin: Confirmation of the Ardeemin Pharmacophore

The MDR chemosensitising activity of several analogues of the ardeemins, including five derivatives of the ABCD fragment, nine derivatives of the complete hexacyclic framework and one seco analogue lacking the B ring was studied. The results obtained confirm that the pharmacophoric moiety of the ardeemins as MDR reversers is located at their DEF fragment, and suggest that the epimer of the ardeemins at the alanine stereocenter should be more active than the natural stereoisomer.