In silico pharmacokinetic profiling, molecular docking, and antioxidant assessment of bis-urea derivatives derived from the sorafenib scaffold

Shoja, Sajede; Gholibegloo, Elham; Mahmoodi, Nosrat O (Allah)

doi:10.22104/mmb.2026.8141.1198

In silico pharmacokinetic profiling, molecular docking, and antioxidant assessment of bis-urea derivatives derived from the sorafenib scaffold

Articles in Press

Document Type : Research Paper

Authors

Sajede Shoja ¹

Elham Gholibegloo ¹

Nosrat O (Allah) Mahmoodi ²

¹ Department of Chemical Technologies, Iranian Research Organization for Science and Technology (IROST)

² Department of Medicinal Organic Chemistry, Faculty of Chemistry, University of Guilan

10.22104/mmb.2026.8141.1198

Abstract

Sorafenib, also known as Nexavar, is a multikinase inhibitor with a diarylurea scaffold. The Food and Drug Administration approved it for the treatment of advanced hepatocellular and renal cell carcinoma. Its well-defined structural framework has served as a template for developing numerous analogs designed to enhance pharmacological efficacy and minimize adverse effects. In this work, seven previously synthesized bis-urea derivatives, for which cytotoxicity (MTT), antibacterial activity, and initial in silico studies have been reported, were further evaluated using molecular docking, in silico ADME studies, and antioxidant assay. These compounds combined diverse linker moieties, enabling structural variations that could modify receptor binding and pharmacokinetic performance. Molecular docking studies of the compounds in complex with selected target receptors, using sorafenib as the positive control, indicated that some derivatives exhibited comparable or improved predicted hydrogen-bond interactions and binding affinities relative to sorafenib. These results reflect computational predictions of ligand–receptor interactions. Pharmacokinetic evaluations were conducted using in silico ADME (Absorption, Distribution, Metabolism, and Excretion) to supplement the docking data. These analyses demonstrated promising characteristics for the target compounds, accompanied by acceptable pharmacological properties, such as balanced lipophilicity, oral bioavailability, and favorable metabolic stability, thus supporting their suitability for further biological assessment. In addition, all compounds were evaluated for their antioxidant activities using standard DPPH assays. Some derivatives showed notable antioxidant effects compared to ascorbic acid as the standard. Pharmacokinetic aspects were evaluated in silico to complement docking studies, while antioxidant activity was explored as an additional physicochemical feature rather than a primary mechanism associated with kinase inhibition.

Keywords

Sorafenib

bis-Urea

Molecular Docking

Pharmacokinetic

ADME

Antioxidant

Subjects