Molecular docking and DFT study of antiproliferative ribofuranose nucleoside derivatives targeting EGFR and VEGFR2in cancer cells.

Autor: Bibi S; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan. Electronic address: shamsa.shafiq@uaf.edu.pk., Urrehaman S; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan., Akram M; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan., Amin R; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan., Majeed H; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan., Khan SR; Department of Chemistry, University of Agriculture, Faisalabad 38000, Pakistan., Younis S; Department of Computer Science, University of Agriculture, Faisalabad 38000, Pakistan. Electronic address: younis.saima@yahoo.com., Bai FQ; Institute of Theoretical Chemistry and College of Chemistry, College of Chemistry, Jilin University, Changchun 130023, China.
Jazyk: angličtina
Zdroj: Computational biology and chemistry [Comput Biol Chem] 2024 Dec; Vol. 113, pp. 108187. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1016/j.compbiolchem.2024.108187
Abstrakt: Antimetabolites are the most effective chemotherapeutics for treating cancer. They have exerted their anticancer effects by interfering with DNA synthesis. Recently, interest in modified nucleoside analogues has grown due to their superior efficiency. Nucleoside analogue derivatives have emerged as crucial candidates for cancer treatment due to their ability to target the cells responsible for cancer within the body specifically. The ability of nucleoside analogues derivatives to target specific molecular pathways has reduced toxicity and increased efficiency compared to traditional chemotherapy drugs. Nucleoside analogues have interfered with physiological nucleosides and induced cytotoxicity in cancerous cells. In this investigation, derivatives of ribofuranose nucleoside analogues have been designed. Density functional theory (DFT) calculations have been performed at the B3LYP/6-311 G(d,p) level. The designed molecules have been characterized by UV/Vis spectroscopy using the CPCM model in DMSO solvent, and molecular structural parameters, such as HOMO/LUMO and MEPS, have been determined. Derivative d1m has exhibited a high energy gap and low absorption energy compared to the other derivatives. Molecular docking of the designed molecules (d1o-d2m) has been performed with the EGFR and VEGFR2 proteins. d2o has shown good binding energy with the EGFR protein, while d1o has shown good results with VEGFR2. Global chemical parameters and NBO analysis have been conducted to investigate the derivatives charge transfer properties and chemical reactivity. NBO analysis has provided information about the donor and acceptor parts within a molecule, while global chemical parameters have given insights into the reactivity, stability, and solubility of the molecules. It has been found that the derivatives are more chemically reactive, thermodynamically stable, and have better binding affinity than the parent molecule. Based on the analysis, the drug interaction with the cancer-causing protein makes it more effective for cancer treatment.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author also declares there is no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: