title: Synthesis and in vitro antitumor activity of new octapeptide analogs of somatostatin containing unnatural amino acids.
abstract: Some modified octapeptide analogs of somatostatin with the following structure D-Phe-c(Cys-Phe-D-Trp-Xxx-Yyy-Cys)-Thr-NH2, where Xxx is Lys or Orn and Yyy is Aib (α-aminoisobutyric acid), Ac5c (1-aminocyclopentanecarboxylic acid) or Ac6c (1-aminocyclohexane carboxylic acid) have been synthesized. The peptides were prepared by standard Fmoc-solid phase peptide chemistry method. The direct disulphide bond formation has been employed on the solid phase by Tl(CF3CO2)3. The cytotoxic effects of the compounds were tested in vitro against a panel of tumor cell lines: HT-29 (human colorectal cancer cell line), MDA-MB-23 (human breast cancer cell line), Hep-G2 (human hepatocellular carcinoma cell line), HeLa (cervical cancer cell line) and normal human diploid cell line Lep-3. The new peptides exhibited different concentration-dependent antiproliferative effect against the tumor cell lines after 24 h treatment. The compounds were most effective to the HT-29 tumor cells. The compound 4C (Orn(5), Aib(6)) demonstrated the most pronounced antiproliferative effects on HT-29 cells with the IC50 = 0.0199 μM.
authors: Institute of Molecular Biology "Roumen Tsanev", Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Bl. 21, 1113, Sofia, Bulgaria.
authors: Svetlana Ts
authors: STs
authors: Staykova
authors: Diana W
authors: DW
authors: Wesselinova
authors: Lyubomir T
authors: LT
authors: Vezenkov
authors: Emilia D
authors: ED
authors: Naydenova
mesh_terms: D000595:Amino Acid Sequence; D000598:Amino Acids, Cyclic / Q000737:chemistry; D000621:Aminoisobutyric Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D003515:Cycloleucine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D060327:Solid-Phase Synthesis Techniques; D013004:Somatostatin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; D000970:Antineoplastic Agents; D003509:Cyclohexanecarboxylic Acids; D009842:Oligopeptides; D003515:Cycloleucine; C100049:2-aminoisobutyric acid; C014966:1-aminocyclohexanecarboxylic acid; D013004:Somatostatin