SYNTHESIS OF (DIALKYLAMINO)ALKYL-DISUBSTITUTED PYRIMIDO[5,6,1-DE]ACRIDINES, A NOVEL GROUP OF ANTICANCER AGENTS ACTIVE ON A MULTIDRUG-RESISTANT CELL-LINE

A series of pyrimidoacridine derivatives with two basic side chains, 7 a-e, was synthesized, as potential antitumor drugs, starting from l]-6 -chloropyrimido[5,6,1-de]acridine-1,3,7-trione (6) and a suitable (alk ylamino)alkylamine. The products 6 and 7a-e showed significant cytotox ic activity in, vitro against L1210 leukemia. Compounds 7a,d were 2 or ders of magnitude more cytotoxic than ametantrone. All compounds were also examined for their activity on LoVo and resistant LoVo/Dx cell li nes. Unlike ametantrone, the compounds have shown to be able to overco me the multidrug resistance. Compounds 7a,d, the two most active in vi tro, were tested in vivo against murine P388 leukemia showing good act ivity.