Synthesis and preliminary biological evaluation of polyamine-aniline acridines as P-glycoprotein inhibitors.

We have synthesized a series of polyamine-based anilinoacridine derivatives. The preliminary biological evaluation indicated that the 9-anilinoacridine- polyamine derivatives had low or insignificant in vitro cytotoxicity against K562 cell line and K562/ADM, the drug-resistant cell line. However, the evaluation for P-gp modulation showed that they held potent P-gp inhibitory ability. Among them, the effect of compound 7c on P-gp was even greater than that of Verapamil, the known P-gp modulator. The results suggest that 9-anilinoacridine- polyamine derivatives can be employed as effective P-gp modulators.