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Drug Res (Stuttg) 2023; 73(06): 355-364
DOI: 10.1055/a-2062-3571
Original Article

Interaction of Some Amino-Nitrile Derivatives with Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Using a Theoretical Model

Lauro Figueroa-Valverde
1   Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Campeche, Camp., México
,
Francisco Díaz-Cedillo
2   Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional. Santo Tomas, México
,
Marcela Rosas-Nexticapa
3   Facultad de Nutrición, Universidad Veracruzana, Médicos y Odontologos, Unidad del Bosque Xalapa Veracruz, México
,
Magdalena Alvarez-Ramirez
3   Facultad de Nutrición, Universidad Veracruzana, Médicos y Odontologos, Unidad del Bosque Xalapa Veracruz, México
,
Maria Virginia Mateu-Armad
3   Facultad de Nutrición, Universidad Veracruzana, Médicos y Odontologos, Unidad del Bosque Xalapa Veracruz, México
,
Maria López-Ramos
1   Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Campeche, Camp., México
,
Tomas López-Gutierrez
1   Laboratory of Pharmaco-Chemistry, Faculty of Chemical Biological Sciences, University Autonomous of Campeche, Campeche, Camp., México
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Abstract

Background Some studies indicate that the angiogenesis process is related to vascular endothelial growth factor, which can interact with endothelial cell surface receptors (VEGF-R1, VEGF-R2, and VEGF-R3); this biochemical process and other factors result in the promotion and growth of new blood vessels under normal conditions. However, some studies indicate that this phenomenon could also occur in cancer cells. It is important to mention that some amino derivatives have been prepared as VEGF-R1 inhibitors; however, their interaction with VEGF-R1 is not clear, perhaps due to different experimental approaches or differences in their chemical structure.

Objective The aim of this study was to evaluate the theoretical interaction of several amino-nitrile derivatives (Compounds 1 to 38) with VEGF-R1.

Methods The theoretical interaction of amino-nitrile derivatives with VEGF-R1 was carried out using the 3hng protein as the theoretical model. In addition, cabozantinib, pazopanib, regorafenib, and sorafenib were used as controls in the DockingServer program.

Results The results showed different amino acid residues involved in the interaction of amino-nitrile derivatives with the 3hng protein surface compared with the controls. In addition, the inhibition constant (Ki) was lower for Compounds 10 and 34 than for cabozantinib. Other results show that Ki for Compounds 9, 10, 14, 27–29 and 34–36 was lower in comparison with pazopanib, regorafenib, and sorafenib.

Conclusions All theoretical data suggest that amino-nitrile derivatives could produce changes in the growth of some cancer cell lines through VEGFR-1 inhibition. Therefore, these amino-nitrile derivatives could be a therapeutic alternative to treat some types of cancer.

Key words

angiogenesis. theoretical model - amino-nitrile - derivatives


Publication History

Received: 22 February 2023

Accepted: 20 March 2023

Article published online:
12 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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