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IN SILICO STUDY OF ALBENDAZOLE MOLECULAR DOCKING WITH VEGFR-2
Shonazar Safayev
3
, Shahnoza Kadirova
2
, Zubayda Abdullayeva
3
1
Doctoral student of Khorezm mamun academy, Uzbekistan, Khiva
e-mail: shonazarsafaev@gmail.com
2
Doctor of chemical sciences, head of the chemistry department, National university of
Uzbekistan, Uzbekistan, Tashkent
3
Doctor of philosophy in chemistry, lecturer, Urgench “Ranch” university, Uzbekistan,
Urgench
Abstract:
This study investigates the molecular docking of albendazole with Vascular
Endothelial Growth Factor Receptor-2 (VEGFR-2), a key protein involved in tumor angiogenesis.
The results revealed multiple binding poses, with the most stable interaction showing a Vina score
of -6.8 kcal/mol, indicating a strong ligand-receptor complex. These findings support albendazole’s
potential role in targeting VEGFR-2-mediated pathways, reinforcing its relevance in cancer
research.
Keywords:
Albendazole, Molecular Docking, VEGFR-2, AutoDock Vina, Angiogenesis, Anti-
Cancer Activity, Benzimidazole, Ligand-Receptor Interaction, Computational Chemistry, Drug
Repurposing.
Molecular docking studies of benzimidazole derivatives have gained attention due to their
diverse biological activities and potential therapeutic applications.
Albendazole, a benzimidazole derivative, primarily exerts its pharmacological effects by
binding to β-tubulin, thereby inhibiting microtubule polymerization. This mode of action has been
supported by several studies, including one where researchers utilized molecular docking to identify
binding sites and affinities of albendazole and its derivatives against mutant and wild-type tubulin
structures. This study indicated that albendazole possesses a robust binding affinity that varied
depending on the mutations present in tubulin [1.252 p.]. Additionally, albendazole has been shown
to disrupt microtubule function, causing cytotoxicity in tumor cells, thereby broadening its
therapeutic implications to include anti-cancer activity [2.877 p.].
Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) plays a pivotal role in tumor
angiogenesis, facilitating the formation of new blood vessels that supply nutrients and oxygen to
tumors, thereby promoting their growth and potential metastasis. Overexpression of VEGFR-2 has
been observed in various cancers, including gastric and ovarian cancers, and is associated with poor
prognosis and increased tumor aggressiveness [3.2 p.].
Molecular docking studies of albendazole has conducted using human Vascular endothelial
growth factor receptor-2 (VEGFR-2 kinase receptor) protein (PDB ID: 3VHE). The protein was
obtained from “Protein data bank” and prepared using Pymol software. Intrinsic water molecules
had removed from protein’s pocket area and polar hydrogens are inserted.
Struture of albendazole is obtained from Pubchem database. AM1 semi-empirical force fields
were used to optimize the ligand structure and converted into pdb format.
This research aims to shed insight on the binding properties of 3VHE protein using
geometrically optimized chemicals like ABZ. Before being employed in molecular interaction
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studies, proteins were checked for missing side-chain residues using the open Molecular Mechanics
(MM) simulation tool. Autodock v 4.2.6 was used for molecular docking investigations.
Vina
Score
(kcal/mol)
Coorinates
(x,y,z)
Cavity
volume
(A
3
)
Active binding sites
-6.8
1, 31, 16
212
Chain A: LEU21 ARG23 VAL25 ALA43 LYS45 GLU58
VAL72 VAL87 VAL89 GLU90 PHE91 CYS92 LYS93
PHE94 GLY95 ASN96 ASP142 ARG146 ASN147
LEU149 CYS159 PHE161
-6.0
10, 32, 3
144
Chain A: SER6 LYS7 TRP8 GLU9 PHE10 PRO11
ARG14 GLY32 ILE33 ASP34 LYS35 LEU62 GLY66
HIS67 ASN73 LEU74 LEU75 GLY76 LYS80 GLU90
-5.7
2, 43, 17
221
Chain A: ARG23 VAL25 ALA43 VAL44 LYS45 LEU47
GLU51 ALA54 LEU55 GLU58 ILE61 LEU62 HIS64
ILE65 VAL72 VAL87 ILE88 VAL89 ASN96 LEU133
LYS137 CYS138 ILE139 HIS140 ARG141 ASP142
ARG146 ASN147 LEU149 CYS159 ASP160 PHE161
PRO162 TYR176
-5.3
10, 27, 12
145
Chain A: GLU27 ILE33 ASP34 CYS39 ARG40 THR41
VAL42 HIS67 LEU69 ASN73 LEU74 LEU75 VAL89
GLU90 PHE91 CYS92 LYS93 SER151 GLU152 LYS153
VAL155 LYS157
Table-1. Vina scores coordinates, cavity volumes and active binding sites of albendazole in with
VEGFR-2 receptor protein in different poses.
In Table 1, we can see that a blind docking analysis was performed using Autodock, in which
albendazole is located in four different poses in the protein cavity. The first column of the table
presents the Vina scores. The smaller the negative value of the Vina score, the higher the protein-
ligand bond strength, and the ligand and protein have a strong interaction in this pose. If we look at
the table, we can see that the Vina scores range from -6.8 to -5.3. The smallest Vina score is -6.8,
which shows the strongest ligand-protein binding in this pose. The second column of the table
presents the coordinates of the ligand in different poses within the protein cavity. The third column
presents the volumes of the protein cavity. The fourth column presents the active binding sites of
the ligand and the protein amino acids. In Figure 1, we can see the binding of the most stable pose
in the protein cavity and the active binding site.
Figure-1. Active binding site of the most stable pose of albendazole and its view in VEGFR-2
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receptor protein cavity
Conclusion.
This study successfully investigated the molecular docking of albendazole with VEGFR-2
using AutoDock Vina. The docking results revealed multiple binding poses, with the strongest
binding interaction observed at a Vina score of -6.8 kcal/mol, indicating a stable ligand-receptor
complex. Key amino acid residues involved in the binding included LEU21, ARG23, VAL25,
ALA43, LYS45, and GLU58, highlighting potential interaction sites critical for VEGFR-2
inhibition. Given VEGFR-2’s role in tumor angiogenesis, these findings suggest that albendazole
may contribute to its reported anti-cancer activity by interfering with VEGFR-2-mediated pathways,
further supporting its potential in cancer treatment.
Referances
1. A. Swargiary, H. Boro, & D. Brahma, "Tubulin-gene mutation in drug resistance in
helminth parasite: docking and molecular dynamics simulation study", Current Chemical Biology,
vol. 17, no. 4, p. 249-259, 2023.
2. N. Dogra, A. Kumar, & T. Mukhopadhyay, "Fenbendazole acts as a moderate microtubule
destabilizing agent and causes cancer cell death by modulating multiple cellular pathways",
Scientific Reports, vol. 8, no. 1, 2018.
3. Lian, L., Li, XL., Xu, MD.
et al.
VEGFR2 promotes tumorigenesis and metastasis in a pro-
angiogenic-independent way in gastric cancer.
BMC Cancer
19, 183 (2019).
