Synthesis and proapoptotic activity of oleanolic acid derived amides

•3-O-Acetyl-OA derived amides have been prepared.•They exhibited fair to good cytotoxicity for several human tumor cell lines.•Picolinylamides acted by autophagy and arrest of the cell cycle in the S phase.•A N-[2-(dimethylamino)-ethyl] derivative triggered apoptosis.•Small structural differences result great differences cytotoxicity of analogs.

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14–16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.

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