Theoretical interaction of muscarinic receptor antagonist with vascular endothelial growth factor receptors (VEGF-R1, R2 and R3) as a therapeutic alternative to treat cancer

Abstract

Several biomolecules have been the target of some drugs for the treatment of cancer; however, there is little information on the interaction of muscarinic antagonists with vascular endothelial growth factor receptor (VEGF-R1, R2, R3). The aim of this research was to determine the possible interaction of muscarinic antagonists such as atropine, ML381, af-dx 386, azaprophen, darifenacin, dicyclomine, PD-102807, pirenzepine, telenzepine, Zamifenacin, and cyclohexylamine with VEGF-R1, R2, and R3. The theoretical interaction of muscarinic antagonists with VEGF-R1, R2, and R3 was carried out using the 2ho4, 3hng, and 4bsj proteins as theoretical tools. Besides, cabozantinib, pazopanib, regorafenib, and sorafenib drugs were used as controls. The results showed differences in the number of aminoacid residues and energy levels involved in the interaction of muscarinic antagonists with 2ho4, 3hng, and 4bsj proteins compared with the controls. Besides, the inhibition constants (Ki) values for atropine, ML-381, zaniferacin, and dicyclomine were lower compared with some controls. In conclusion, the results suggest that atropine, ML-381, zaniferacin, and dicyclomine could act as VEGF receptor inhibitors, could result in changes in the biological activity of angiogenesis, and this phenomenon could be translated as a decrease in cancer cell growth. Therefore, these drugs could be a good therapeutic alternative to evaluate their biological activity in some cancer models