Structure Activity Studies on the Crinane Alkaloid Apoptosis-inducing Pharmacophore

The apoptosis-inducing ability of alpha-ethano bridged crinane alkaloids was investigated using natural and semi-synthetic derivatives uncovering novel structural requirements of this cytotoxic pharmacophore. An alpha-ethano bridge is required; an alpha- or beta-methoxy or hydroxyl H-bond acceptor are all tolerated at C-3; a small substituent (H, or OH) alone is tolerated at C-11; and a C-1 to C-2 double bond is shown to modulate, but is not a requirement for, apoptosis-inducing activity.