Prostate cancer will affect one in eight men during their lifetime and is the fifth leading cause of cancer related deaths in men. Conventional treatments for prostate cancer include androgen-deprivation therapy, however, most men treated with androgen-deprivation therapy progress to hormone-refractory prostate cancer. There are currently no curative treatments for hormone-refractory prostate cancer. Cyclopropabenzindoles (CBI) are more biologically potent and synthetically accessible analogues of the cyclopropapyrroloindole (CPI) anti-tumour antibiotics, such as duocarmycin-SA and CC1065. Seco-amino-CBIs can be incorporated into a polymeric prodrug system that will release the seco-amino-CBIs at the site of tumour selectively. The polymeric prodrug system consists of linear polyethyleneglycol (20 KDa) bound to a PSA-cleavable linker peptide to which the seco-amino-CBI is attached. The prodrug has two modes of selectivity: activation by PSA and the EPR effect. The synthesis of a range of seco-amino-CBI compounds was performed in order to investigate the structure- activity relationship surrounding the non-alkylating DNA minor-groove binding subunit. A novel synthetic route was developed to bypass issues surrounding the required orthogonal protection of two amine groups. This route provided access to a range of seco-nitro-CBIs that were further investigated as hypoxia-activated prodrugs. Biological evaluation of the seco- nitro-CBIs and seco-amino-CBIs was investigated through DNA-melting assays which confirmed the ability of the seco-amino-CBIs to bind covalently to DNA. MTS-assays were carried out to evaluate the relative cytotoxicity’s of the range of seco-nitro-CBIs and seco- amino-CBIs. Novel compound (5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indol-3- yl)(5-hydroxy-1H-indol-2-yl)methanone showed exquisite potency, with a determined IC50 value of 1.5 nM against PC3 cells. MTS-assays performed under hypoxic conditions allowed the investigation into the suitability of the seco-nitro-CBIs as hypoxia-activated prodrugs. (1- (chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-3-yl)(5-hydroxy-1H-indol-2- yl)methanone exhibited a hypoxia-cytotoxicity ratio of 2.34.