New cyclic somatostatin analogues containing a pyrazinone ring: importance of Tyr for antiproliferative activity

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6199-201. doi: 10.1016/j.bmcl.2008.10.001. Epub 2008 Oct 5.

Abstract

Novel somatostatin analogues containing a pyrazinone ring, compounds 1 and 2, exhibited good antiproliferative activity on A431 tumor cells. To increase antitumor activity and binding affinity on somatostatin receptors (SSTRs), we substituted Tyr in the critical sequence, Tyr-D-Trp-Lys, with more hydrophobic aromatic residue. The substituted compounds dramatically lost antitumor activity, indicating that Tyr residue was an essential residue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Pyrazines / chemical synthesis*
  • Pyrazines / chemistry
  • Pyrazines / pharmacology*
  • Receptors, Somatostatin / drug effects*
  • Somatostatin / analogs & derivatives
  • Somatostatin / chemical synthesis
  • Somatostatin / chemistry
  • Somatostatin / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tyrosine / chemistry
  • Tyrosine / pharmacology*

Substances

  • Antineoplastic Agents
  • Pyrazines
  • Receptors, Somatostatin
  • Tyrosine
  • Somatostatin