Synthesis and cytotoxic activity of benzo[a]acronycine and benzo[b]acronycine substituted on the A ring.

Abstract The impact of substitutions at position 10 in the A ring of the cytotoxic benzo[ a ]acronycine and benzo[ b ]acronycine series has been explored. 10-Bromobenzo[ a ] and 10-bromobenzo[ b ]acronycine were prepared in 12% and 15% yield respectively from commercially available chemicals. Their 1,2-dihydro-1,2-dihydroxy diesters were synthesized. The different derivatives were tested against two cell lines KB-3-1 and L1210. Their cytotoxic activities were found in the same range of magnitude as their non-substituted counterparts. These structure–activity relationships permitted to conclude that the introduction of a substituent at position 10 maintains the activity in both the benzo[ a ] and [ b ]acronycine series and open the way to further pharmacomodulations.