Résumé

A number of cyclo-β-tripeptides and their linear precursors were subjected to primary biol. evaluation for cancer-cell growth inhibition (one-dose, three-cell essay), and the five most active ones were then tested in the anti-tumor screen of the National Cancer Institute (Bethesda, USA) with 60 human cancer cell lines. Growth inhibition values GI50 in the one-digit micromolar, and in one case in the nanomolar range were obtained. The effects show selectivities for certain types of cancer cells and for certain cell lines within these types; the screen includes leukemia, non-small-cell lung, colon, and central-nervous-system (CNS) cancer, melanoma, ovarian, renal, prostate, and breast cancer cell lines. The synthesis and full characterization of two new cyclo-β-peptides,(β3-HSer(OBn))3 (I; R = β-CH2OCH2Ph) and (β3-HMet)3 (I; R = β-CH2CH2SMe) are described. Other cyclo-β-peptides included in this investigation are (β-Asp(Bn))3 (I; R = α-C(O)OCH2Ph), (β-HGlu(Bn))3 (I; R = β-(CH2)2C(O)OCH2Ph), and (β-HAla)3 (R = β-CH3), compounds which had been previously prepared by us. Strongest activities were measured with the cyclo-β-peptides bearing benzyl-ester or benzyl-ether groups in the side chains. The cytotoxic activity of the compds. included in this investigation is much lower (LC50>100 μM) than their antiproliferative activity (GI50).

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