Synthesis, DNA binding and topoisomerase inhibition of mononaphthalimide homospermidine derivatives

Two novel mononaphthalimide homospermidine derivatives (2a, 2b) with three or four methylene unit as linkages were synthesized and evaluated for cytotoxicity against human leukemia K562, murine melanoma B16 and Chinese hamster ovary CHO cell lines. The presence of homospermidine motif could greatly elevate the potency of 1,8-naphthalimide. Conjugate 2b with longer spacer exhibited higher in vitro cytotoxicity than 2a. The DNA binding experiments indicated that conjugates 2b could bind to herring sperm DNA. The topoisomerase II poison trials revealed that 2b could inhibit the activity of top. II.