Series of 4-(ethylsulfonyl)-1-halogen-2-nitrobenzene (3a–e) and 1-(4-halogen-3-nitrophenyl) propan-1-one (5a–d) analogs designed as novel radiosensitizers using bromonitropropiophenone and bromonitrobenzonitrile as lead compounds were synthesized. The anticancer activities of the compounds were evaluated in vitro using human prostate cancer (DU-145) and breast cancer (MCF-7) cell lines and the MTT assay. From the series, six compounds (3b–e, 5b–c) exhibited potent growth inhibitory effects against both cell lines. The most active, compound 3d, is an iodosulfone and is significantly more potent than the lead compound 5c at 10 μm. Compounds were then compared with doxorubicin, a clinically used anticancer compound for breast and prostate cancers. Our most active compound 3d is more effective than doxorubicin at the dose level of 10 μm at 3 days after radiation, cell viabilities of 18%, 13% compared to 87%, 94% against MCF-7, and 15%, 20% compared to 60%, 75% against DU-145 without and with radiation, respectively. At 10 μm, compound 5c had no effects as compared to control, whereas compound 3d reduced DU-145 cell viability to 16% and that of MCF-7 cells to 9% even at 5 days after radiation. These results are very encouraging. Future studies include testing the compounds in vivo with and without radiation.