The inventors have synthesized a set of structurally diverse natural and synthetic ETP alkaloids to study the SAR of ETP-containing natural products and their synthetic cognates and to determine which ETP derivatives demonstrate the most potent anticancer activity. Monomeric and dimeric ETP alkaloid derivatives were created by constructing compounds that varied in the substituents about the hexa-hydropyrroloindoline carboskeleton and the nature, extent and configuration of sulfuration. Sixty natural alkaloids and their derivatives were then tested for their ability to induce cell death in two human cancer cell lines: U-937 (leukemic monocyte lymphoma) and HeLa (cervival cancer). The most potent derivatives from this primary screening were tested in vitro against a panel of three supplementary human cancer cell lines: H460 (lung carcinoma), 786-O (renal carcinoma) and MCF-7 (breast carcinoma). Representative compounds from the monomer and dimer classes were shown to induce caspase-dependent apoptosis. The potent and broad anticancer activity of ETP-containing alkaloids suggests that they have considerable translational potential in treating cancer.