Two new imidazophenanthroline derivatives, namely 2-(4-bromo-(2,1,3)-benzothiadiazol-7-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (btdip), 2-(dibenzofuran-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (dbfip) and their octahedral nickel complexes [Ni(phen)(2)(btdip)](2+) (1) and [Ni(phen)(2)(dbfip)](2+) (2) have been synthesized and characterized by CHN analysis, ESI-MS, NMR and UV-vis spectra. Their DNA binding abilities were spectrophotometrically, hydrodynamically and electrophoretically studied and found that while btdip binds DNA externally, dbfip binds in the grooves and both of their nickel complexes also bind DNA through grooves giving severe DNA damage in the presence of peroxide. The compounds were screened against four different human cancer cell lines using MTT assay method. The results obtained showed that both ligands are active against DLD-1, and further dbfip is found to be more active than positive control drugs against DLD-1 and HepG2 cell lines. The complex 2 has more antiproliferative effect than 1 against MCF-7 and HepG2 cells. On the other hand, complex 2 was found to have more toxic effect on HepG2 cells than the standard drugs cisplatin and ploxal-S.