In Vitro and In Silico Evaluation of Antiproliferative Activity of New Isoxazolidine Derivatives Targeting EGFR: Design, Synthesis, Cell Cycle Analysis, and Apoptotic Inducers

A series of novel enantiopure isoxazolidine derivatives were synthesized and evaluated for their anticancer activities against three human cancer cell lines such as breast carcinoma (MCF-7), lung adenocarcinoma (A-549), ovarian (SKOV3) by employing MTT assay. The compounds characterized NMR elemental analysis. Results revealed that all the displayed significant inhibition towards tested lines. Among them, 2g 2f, which differ only presence an ester group at C-3 position small EDG (methyl) C-5 phenyl ring (2g), most active in attenuating growth cells a dose-dependent manner. IC50 17.7 ± 1 µM 12.1 1.1 13.9 0.7 (SKOV3), 2f 9.7 1.3µM 0.7µM 6.5 0.9µM respectively, comparable to standard drug, doxorubicin. enzymatic EGFR afforded good inhibitory activity with 0.298 0.007 μM 0.484 0.01 µM, close positive control, Afatinib. Compound arrested cycle S phase MCF-7 SKOV3 cells, G2/M A549 cell; however, induced G0/G1 arrest, inhibited progression together apoptotic effects. docking study into ATP-active site it fits nicely binding affinity. pharmacokinetic drug-likeness scores notable lead-like properties. At 100 ns, dynamic simulation investigation high conformational stability cavity.