Synthesis, in vitro biological activity, hydrolytic stability and docking of new analogs of BIM-23052 containing halogenated amino acids.

Amino Acids
Dancho DanalevEmilia Naydenova

Abstract

One of the potent somatostatin analogs, BIM-23052 (DC-23-99) D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2, has established in vitro growth hormone inhibitory activity in nM concentrations. It is also characterized by high affinity to some somatostatin receptors which are largely distributed in the cell membranes of many tumor cells. Herein, we report the synthesis of a series of analogs of BIM-23052 containing halogenated Phe residues using standard solid-phase peptide method Fmoc/OtBu-strategy. The cytotoxic effects of the compounds were tested in vitro against two human tumor cell lines-breast cancer cell line and hepatocellular cancer cell line, as well as on human non-tumorigenic epithelial cell line. Analogs containing fluoro-phenylalanines are cytotoxic in μM range, as the analog containing Phe (2-F) showed better selectivity against human hepatocellular cancer cell line. The presented study also reveals that accumulation of halogenated Phe residues does not increase the cytotoxicity according to tested cell lines. The calculated selective index reveals different mechanisms of antitumor activity of the parent compound BIM-23052 and target halogenated analogs for examined breast tumor cell lines. All peptides tested have high a...Continue Reading

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