Oxazinyl-Thiazolidinone Hybrids: Integrated synthesis, Anticancer activity, Molecular docking, and In-silico Pharmacokinetic evaluation

A series of 3-(6-(furan-2-yl)-4-(4-nitrophenyl)-6H-1,3-oxazin-2-yl)-2-phenylthiazolidin-4-one derivatives (15–19) were synthesized via a silica-supported method and comprehensively characterized using FT-IR, 1 H and 13 C NMR, and mass spectrometry. The anticancer potential of these thiazolidinone.oxazine hybrids was evaluated against the MCF-7 breast cancer cell line using the MTT assay. All compounds displayed moderate cytotoxic activity, with IC 50 values ranging from 51.20 to 87.10 µM. Among them, the nitrosubstituted compound 15 exhibited the highest cytotoxic potency (IC 50 = 51.20 µM), which may be attributed to the electron-withdrawing effect of the nitro group. To rationalize the experimental findings, molecular docking studies were performed against key breast cancerrelated targets, including the estrogen receptor (2IOK), HER2 (7PCD), EGFR/SRC (1QCF), and HSP90 (8B7J). The docking results revealed strong binding interactions for all compounds, with compound 16 showing the highest docking affinity, while compound 15 demonstrated superior in-vitro cytotoxicity, highlighting the complementary nature of computational and biological evaluations. Furthermore, in silico ADME and toxicity analyses indicated favorable pharmacokinetic profiles, acceptable oral bioavailability, and moderate predicted toxicity. All compounds satisfied Lipinski’s Rule of Five, falling within the optimal drug-like molecular weight range (200–500 g/mol), except compound 16. Overall, the combined experimental and computational results underscore the potential of oxazinyl–thiazolidinone scaffolds as promising lead candidates for the development of novel antibreast cancer agents.