Synthesis and cytotoxicity of 3-aryl acrylic amide derivatives of the simplified saframycin–ecteinascidin skeleton prepared from l-dopa

Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified saframycin–ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from l-dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure–activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC50 value of 50 nM.

Twenty four simplified saframycin–ecteinascidin derivatives were synthesized. The cytotoxic activities of these compounds were screened and the structure–activity relationship was discussed.Figure optionsDownload as PowerPoint slideHighlights
► Twenty-four simplified saframycin–ecteinascidin analogs were prepared.
► Their structures were confirmed through NMR and HRMS.
► Their cytotoxicity were screened.
► Most compounds showed potent cytotoxicity.