Work

Discovery of bis -chalcones and bis -pyrimidines as potential urease inhibitors: from synthesis to computational insights

Year: 2025

Type: article

Abstract: AIMS: -pyrimidines as potential urease inhibitors. MATERIALS AND METHODS: urease inhibitory activity. Kinetic studies were conducted using Lineweaver-Burk plots to determine the inhibition mechanism of the most potent compound. Molecular docking was employed to investigate the binding interactions with the urease active site, followed by MD simulations to validate complex stability. Computational ADMET analysis was performed to assess the drug-like properties of the most active inhibitor. RESULTS: Several synthesized compounds exhibited potent urease inhibitory activity, significantly surpassing the standard inhibitor thiourea. The most active compound, 8P, displayed noncompetitive inhibition, as confirmed by kinetic studies. SAR analysis revealed that electron-withdrawing substituents enhanced inhibitory potency. Molecular docking studies demonstrated favorable interactions between inhibitors and key urease residues, while MD simulations confirmed complex stability. ADMET analysis supported the drug-like potential of 8P. CONCLUSIONS: This study provides valuable insights into the development of target compounds as promising urease inhibitors. These findings suggest their potential therapeutic applications for urease-related disorders.

Source: Future Medicinal Chemistry

DOI: 10.1080/17568919.2025.2485870

Authors: Nafeesa Naeem, Sumera Zaib, Ehsan Ullah Mughal, Gehan Ahmed Othman, Amina Sadiq, Nehal Rana

Institutions: University of Gujrat, University of Central Punjab, King Khalid University, Government College Women University Sialkot

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: King Khalid University

Award: G4925177401