Synthesis and Exploration of Anticancer Potential of Baylis–Hillman Derived Oxindole–Chalcone Derivatives

Herein, our research goes to cover how oxindole–chalcones are transformed into Baylis–Hillman products using the Lewis base catalysis and reporting their anticancer screening outcomes. Actually, oxindoles and chalcones showed the strong anticancer effects as per preceding research reports. Therefore, we chose to synthesis of α-OH-containing oxindole–chalcone derivatives using the Baylis–Hillman reaction, and the structure was elucidated using FT-IR_cm-1, ¹H and ¹³C-NMR_ppm, and HRMS_m/z. Moreover, the druglikeness properties of synthesized compounds were analyzed using ADME/T scores. For in silico analysis, caspase-3, and PARP proteins were utilized to the formation of molecular docked complexes to finding their binding affinities, consequently, S5, S9, S11, and S15 exhibited the strongest binding affinities, with energies of −8.7, −8.5, −8.4, and −8.4 kcal/mol, respectively as well. In the same context under in vitro analysis, compounds were tested against U87 glioblastoma cancer cell line at different concentrations. As per results, the synthesized compound S5 showed best activity (IC₅₀ = 100.5 ± 34.42 µM) against U87 glioblastoma. Further confocal microscopy and western blotting revealed the apoptosis inducing nature of these compounds specially modulating through the Bax/Bcl2 and PARP regulation and evaluated the anticancer effects. Futuristically, more research is needed to enhance their potency and selectivity, as well as assess their in vivo performance in glioblastoma models.