New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC<sub>50</sub> = 0.59 ± 0.27 µM) was observed to be 11 times more active than PPA (IC<sub>50</sub> = 6.5 ± 0.30 µM) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC<sub>50</sub> = 0.9 ± 0.05 µM) and A549 (IC<sub>50</sub> = 100 ± 7.0 µM) cell lines, respectively.