Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs

Abstract

Context: Inhibition of pathological angiogenesis.

Objective: Obtaining new transactivator, bifunctional, thyroid antagonist, non-toxic anti-angiogenic compounds.

Materials and methods: In silico drug design, synthesis in bulk and biological evaluation in chick chorioallantoic membrane (CAM) model.

Results: Significant inhibition (range 65–73%) at 0.25–2.0 µg/ml doses.

Discussion and conclusion: The synthesis of compounds (9), (10), and (11) incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions, respectively, into the core molecular framework of tetrac (tetraiodothyroacetic acid) were undertaken. The evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity in comparison with tetrac and XT199, which showed nearly 86% inhibition at dose levels of 1 and 0.5 µg/ml, respectively, and validated the concept.

Keywords::

• Antiangiogenesis
• XT199
• dual thyrointegrin antagonist
• molecular modelling
• chick chorioallantoic membrane assay