Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives

The synthesis of new acridinone and dioxophenothiazine derivatives along with their tubulin polymerization inhibitory and antiproliferative activities is reported. The analysis of correlation for cytotoxic and antitubulin potential of tested compounds showed that 4-methoxyphenylethyl derivatives 18a and 19a were highly cytotoxic but were regarded to have no significant antitubulin activity. However, the introduction of a 3-hydroxy substituent leading to compounds 18e and 19e, strongly increased the antitubulin potential but was associated with a loss of the antiproliferative activity. Modeling studies, topoisomerase inhibition assays and cell cycle analysis have been performed to better investigate the mechanism of action of such compounds.

Graphical abstractThe synthesis of new acridinone and dioxophenothiazine derivatives along with their tubulin polymerization inhibitory and antiproliferative activities is reported.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The synthesis of new acridinone and dioxophenothiazine derivatives is described. ► These compounds were tested for their antitubulin and anti-proliferative activities. ► Modeling studies explained the potent antitubulin activity of some of them. ► Pharmacological assays were performed to understand their mechanism of action.