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

作者：Bridoux Alexandre; Khan Riaz A; Chen Celei; Cheve Gwenael; Cui Huadong; Dyskin Evgeny; Yasri Aziz; Mousa Shaker A^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, 26(6): 871-882.

DOI：10.3109/14756366.2011.557023

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

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 mu g/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 mu g/ml, respectively, and validated the concept.

• 出版日期2011-12