Several derivatives of the natural scabrosin esters were synthesized in order to elucidate the structural features present, which are responsible for the biological activities. The studies demonstrate that full anti-proliferative activities of the scabrosin esters, both the carboskeleton core as well as the ability to form the dithiol and/or the disulfide linkage of the epidithiopiperazine-2,5-dione are required. The presence of the epoxide rings on the scabrosin esters do not contribute to the observed biological activities.