Experimental antileukemic agents. Coralyne, analogs, and related compounds

Article abstract of DOI:10.1021/jm00249a020

Analogs of the antileukemic alkaloid coralyne and related compounds were synthesized for structure activity study. It was found that among the 8 alkyl substituted and the 8 unsubstituted compounds, the 8 ethyl homolog demonstrates better antileukemic activity against leukemias L1210 and P388 in mice than the parent compound; the 8 propyl derivative is inactive, suggesting that both lipid solubility and steric effect are significant factors; the planarity and rigidity of molecules of this type are critical to activity; replacement of either or both o dimethoxy groups of coralyne by methylenedioxy groups causes a slight decrease in the antileukemic activity; interestingly, the two bis(methylenedioxy) analogs displayed activity in the KB cell culture system whereas the corresponding dimethoxy compounds are inactive; elimination of some methoxy groups of coralyne lowers, but does not completely abolish, the original activity; and activities of different salts are comparable but the acetosulfate salt is preferred because of its relatively higher solubility in water. Coralyne forms a stable complex with thymus DNA in vitro and exhibits reversible covalent hydration in water. The activity of coralyne against leukemia L1210 was shown to be schedule independent.