Flavonoid–Antibiotic Synergy: A Review of in Vitro Evidence and Molecular Docking Studies

Due to the worldwide emergence of antimicrobial resistance, plant-based natural compounds, especially flavonoids, are becoming increasingly attractive for the development of new antimicrobial drugs. In this narrative review, the potential of combining in vitro assays of plant flavonoids antibacterial and synergistic activity with in silico molecular docking is examined to gain a better insight into their possible mechanisms of action. This review focuses on publications from 2021 to 2026 in the scientific literature that have been indexed in major databases, especially Scopus and PubMed, which also include computational computational modeling studies based on AutoDock Vina, along with the assessment of biological activity. Based on the literature reviewed, the use of computational methods in pharmacognosy drug discovery can be beneficial to identify and prioritize bioactive compounds, thereby saving time and resources for preliminary screening. The molecular docking analysis offers useful predictions of ligand–target interactions, binding orientations and binding affinities that can shed light on the observed antibacterial activity in experiments. Predicted binding energies however should be used in conjunction with experimental evidence and not as a clear indicator of biological activity or synergism. In conclusion, it can be said that this study has highlighted the importance of the scientific value of using both the experimental study and the structure-based computational study to enhance the evaluation of plant flavonoids as antibacterial agents. It also emphasizes the need for uniform extraction methods, antimicrobial evaluation and molecular docking studies to ensure reproducibility and comparability of results. Therefore, molecular docking is suggested as a complementary screening tool for prioritizing some of the promising phytochemicals of the identified compounds for further detailed experimental validation.