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

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of 10-bromo-1,2-dihydrobenzo[a]acronycine diesters. ► Synthesis of 10-bromo-1,2-dihydrobenzo[b]acronycine diesters. ► Cytotoxic activities of 10-bromobenzo[a] and [b]acronycine series. ► Brome at position 10 maintains the activity of the benzo[a] and [b]acronycine series.