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.
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