Abstract

MOLECULAR DOCKING AND PHARMACOKINETIC PROFILING OF 2,4-DISUBSTITUTED FURAN DERIVATIVES AGAINST PROTEIN 7UR3 FOR ANTICANCER ACTIVITY

Mrs. Sarala A.*, Mr. Senthil Kumar S. K., Ms. Keerthika S., Mr. Krishnaraj A., Ms. Krishnaveni G., Ms. Lokeshwari K., Mrs. Madhupriya V.

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Abstract

Objectives: The present study was undertaken to evaluate the anticancer potential of 2,4-disubstituted furan derivatives through molecular docking against protein 7UR3 using SwissDock and AutoDock software, along with ADME parameter analysis to identify drug-like candidates. Methods: A set of 2,4-disubstituted furan derivatives was designed and energy-minimized. The crystal structure of protein 7UR3 was retrieved from the RCSB Protein Data Bank, prepared by removal of non-essential water molecules, addition of polar hydrogens, and charge assignment. Docking was performed using SwissDock and AutoDock 4.2 (Lamarckian Genetic Algorithm) targeting the active site residues. Pharmacokinetic profiling, including Lipinski’s rule of five, logP, gastrointestinal absorption, P-gp substrate prediction, and cytochrome P450 inhibition, was assessed using SwissADME. Results: Compounds 1, 3, 15, 16, and 17 showed higher binding affinity towards 7UR3 compared to other tested derivatives, with favorable docking scores in both SwissDock and AutoDock. These compounds exhibited stable interactions, including hydrogen bonding and hydrophobic contacts with key active site residues. ADME profiling revealed compliance with Lipinski’s rule, high predicted gastrointestinal absorption, and absence of major CYP inhibition liabilities. Conclusion: In-silico molecular docking binding affinity towards 7UR3 compared to other tested derivatives, with favorable docking scores in both SwissDock and AutoDock. These compounds exhibited stable interactions, including hydrogen bonding and hydrophobic contacts with key active site residues. ADME profiling revealed compliance with Lipinski’s rule, high predicted gastrointestinal absorption, and absence of major CYP inhibition liabilities. Conclusion: In-silico molecular docking combined with ADME analysis suggests that compounds 1, 3, 15, 16, and 17 are promising 7UR3 binders with favorable pharmacokinetic properties, warranting further synthesis and biological evaluation for anticancer activity.

Keywords: 2,4-disubstituted furan, molecular docking, SwissDock, AutoDock, ADME, anticancer activity, 7UR3.