Fe₃ O₄ nanoparticles mediated synthesis of novel spirooxindole-dihydropyrimidinone molecules as Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is a validated molecular chaperone considered as the new key recipient for cancer intervention. The current study illustrates the synthesis of novel spirooxindole-dihydropyrimidinones (4a-j) by Fe₃ O₄ nanoparticles intervened synthesis and their Hsp90 ATPase inhibitory activity was investigated by the malachite green assay. All the compounds in the study demonstrated a moderate to potent ATPase inhibitory profile, with IC₅₀ values ranging from 0.18 to 6.80 μM. Compounds 4j, 4h, 4f, and 4i exhibited maximum inhibitory potential with IC₅₀ values of 0.18, 0.20, 0.35, and 0.55 μM, respectively. They were found to be better than the standard drug, geldanamycin (Hsp9 ATPase inhibition IC₅₀  = 0.90 μM). Compounds 4h and 4j with IC₅₀ values of 22.82 ± 0.532, 20.78 ± 0.234 and 21.32 ± 0.765, 28.43 ± 0.653 µM showed significantly greater potencies against the MCF-7 and HepG2 cell lines, respectively. Compound 4j showed good antioxidant activities in the DPPH test and H₂ O₂ assay (IC₅₀  = 20.13.23 ± 0.32 and 23.27 ± 0.32 μg/mL) when compared with the standard ascorbic acid (IC₅₀  = 19.16 ± 0.20 and 20.66 ± 1.09 μg/mL). A molecular docking study was performed to observe the binding efficiency and steric interactions of the lead moiety.