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  2. Synthesis of new analogs of tetraiodothyroacetic acid (tetrac) as novel angiogenesis inhibitors for treatment of cancer

Synthesis of new analogs of tetraiodothyroacetic acid (tetrac) as novel angiogenesis inhibitors for treatment of cancer

  • Bioorg Med Chem Lett. 2018 Apr 15;28(7):1223-1227. doi: 10.1016/j.bmcl.2018.02.045.
Mehdi Rajabi 1 Murat Yalcin 2 Shaker A Mousa 3
Affiliations

Affiliations

  • 1 The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
  • 2 The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA; Department of Physiology, Veterinary Medicine Faculty, Uludag University, Bursa, Turkey.
  • 3 The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA. Electronic address: [email protected].
Abstract

In the angiogenesis process, integrins, which are members of a family of cell surface transmembrane receptors, play a critical role particularly in blood vessel formation and the local release of vascular growth factors. Thyroid Hormones such as l-thyroxine (T4) and 3,5,3'-triiodo-l-thyronine (T3) promote angiogenesis and tumor cell proliferation via Integrin αvβ3 receptor. At or near an arginine-glycine-aspartate (RGD) recognition site on the binding pocket of Integrin αvβ3, tetraiodothyroacetic acid (tetrac, a deaminated derivative of T4) is a thyrointegrin receptor antagonist and blocks the actions of T3 and T4 as well as different growth factors-mediated angiogenesis. In this study, we synthesized novel tetrac analogs by modifying the phenolic moiety of tetrac and tested them for their anti-angiogenesis activity using a Matrigel plug model for angiogenesis in mice. Pharmacological activity results showed that tetrac can accommodate numerous modifications and maintain its anti-angiogenesis activity.

Keywords

Angiogenesis; Integrin; Tetrac; Tetraiodothyroacetic acid; Thyroid hormones.

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