Synthesis and cytotoxicity of 1-phenylethanolamine carboxamide derivatives: effects on the cell cycle

Seven novel analogues of 1-phenylethanolamine carboxamide derivatives, 3a–3g, related to carboxamides isolated from Isodon excisus were synthesized and evaluated for their cytotoxic and apoptosis-induction properties against murine B16 and leukemia L1210 cell lines. Compounds containing no substitution at the 4′-position (3a–3d) or containing a 4′-amino (3e–3g) group were investigated. Generally, the amino-containing compounds were slightly more active than their unsubstituted congeners. Also, the indole-containing compounds 3c and 3f gave the strongest cytotoxic activity (IC₅₀ = 25–87 μM) against the growth of L1210 and B16 cancer cells. Compound 3f was subjected to flow cytometry studies and it was found to induce L1210 cells grown in culture to undergo apoptosis.