Structural modification study of anthracyclinones: synthesis and biological activity of several derivatives of...

On the basis of the N-O-O triangular pharmacophore hypothesis postulated earlier in our laboratory, selected side chains with or without the nitrogen atom at the strategic position were incorporated to eta-pyrromycinone, one of the anthracyclinones derived from the antibiotic cinerubins. Since none of the anthracyclinones (the aglycones of anthracyclines) were reported to have antineoplastic activity, the validity of the proposed hypothesis could be tested. Results indicated that a compound designed in this manner, 1,4-bis[2-(2,2-dimethyloxazolidin-3-yl)ethylamino]-1,4-didehydr oxy-eta- pyrromycinone (9c) possessed both in vitro and in vivo antineoplastic activity comparable to that of mitoxantrone. The structure-activity relationship of this class of compounds is discussed.