Design, synthesis and growth inhibition activity of bis-epoxyethyl derivatives of stallimycin modified on the amidino moiety

Derivs. I [R = H, X = NCN (3) or NOH (4); X = O, R = H (5) or Me (6)] of stallimycin (distamycin A) modified at the C-terminal amidine moiety and tethered to a bis-epoxyethyl moiety (as DNA alkylating unit) at the N-terminal position have been prepd. and tested for in vitro cytotoxic activity against two different leukemic cell lines, K562 and L1210. None of the compds. without epoxide was active. A comparison of the biol. activity related to the diepoxy compds. 3-6 with different non-basic amidine modified moieties, showed low activity for the carbamoyl and N-Me carbamoyl derivs. (compds. 5 and 6, resp.), moderate activity for the amidoxime analog 4, and good activity for the cyanamidine deriv. 3.