In silico screening, molecular docking, SAR and toxicity prediction of phenyl-substituted furoic acid derivatives as potential dual-target candidates targeting COX-2 and GABAA receptors

A series of 5-phenyl-2-furoic acid derivatives was investigated using computational approaches to explore their potential interactions with COX-2 and GABA A receptors. Aim: To design and evaluate a focused library of 5-phenyl-2-furoic acid derivatives for their binding characteristics toward COX-2 (PDB ID: 1CX2 ) and GABA A receptor (PDB ID: 8BEJ ) and to explore potential dual-target interactions through in silico analysis. Background: Chronic pain and anxiety frequently coexist and often require multi-target therapeutic approaches. Heteroaromatic scaffolds such as furan derivatives are widely used in medicinal chemistry and provide a suitable framework for computational multi-target design. Body: A total of 33 derivatives were constructed in silico and screened using a standardized PyRx/AutoDock Vina docking protocol. The docking method was validated by redocking native ligands, yielding RMSD values of 2.4 Å for COX-2 and 2.1 Å for the GABA A receptor. Selected top-ranked compounds were further analysed using molecular dynamics (MD) simulations to evaluate the stability of protein–ligand complexes. The MD results, including RMSD, RMSF, radius of gyration, hydrogen bonding and energy analysis, appeared to indicate stable structural behavior of the complexes during the simulation period. Docking results may suggest favourable binding interactions for compounds R18 and R7 across both targets. Conclusion: The findings provide computational insight into the potential dual-target interactions of 5-phenyl-2-furoic acid derivatives. However, further experimental validation is required to confirm these observations.