Solvent Effects, Druglikeness, Pharmacokinetics/ADMET and Neuronal Pentraxin-1 and Contactin-2 Targeted Molecular Docking Investigations of Potential Antitumor Agent 5-Ethynyl-2'-deoxyuridine

Abstract

Glioblastoma (GBM) is an aggressive brain tumor associated with increasing annual morbidity and mortality rates. Standard treatment typically involves surgical resection followed by postoperative Temozolomide (TMZ). Recently, 5-Ethynyl-2'-deoxyuridine (EdU) has been reported to demonstrate significant antitumor effects against GBM. Therefore, this study investigated the potential of EdU to activate apoptotic pathways in astrocytes carrying mutant DNA a key factor in GBM formation and evaluated its therapeutic efficacy at the molecular level. The investigation was conducted using molecular docking analyses. The neuronal membrane protein contactin-2 (PDB ID: 2OM5), encoded by the CNTN2 gene, and NPTX1 (PDB ID: 6YPE), a protein highly expressed in the brain, were selected as target receptors. Additionally, the solvation behavior, drug-likeness, pharmacokinetic parameters, and toxicity profiles of EdU were determined and compared with those of the widely prescribed antitumor agent, TMZ. Results indicated that EdU interacted with the 2OM5 receptor at residues Asp184 and Ser186, and with the 6YPE receptor at residues Trp258, His314, Asn380, Trp409, Ser403, and Asp226. Moreover, EdU exhibited a 7.5% higher binding affinity for 2OM5 and 3.0% higher binding affinity for 6YPE compared to TMZ. Furthermore, the LD₅₀ value of EdU was found to be significantly higher than that of TMZ, indicating a much lower toxicity profile. These findings suggest that EdU is a highly promising candidate for the treatment of GBM. 

Keywords

• Solvent effects
• Molecular docking
• In silico drug investigations
• EdU

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