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

MADDELA S, MAKULA A, GALIGNIANA MD, PARAMBI DGT, FEDERICCI F, MAZAIRA G, HENDAWY OM, DEV S, MATHEW GE, MATHEW B

ARCHIV DER PHARMAZIE

John Wiley Library

Año: 2019 vol. 352

1521-4184

Heat shock protein 90 (Hsp90) is a validated molecular chaperone considered asthe new key recipient for cancer intervention. The current study illustrates thesynthesis of novel spirooxindole-dihydropyrimidinones (4a?j) by Fe3O4 nanoparticlesintervened synthesis and their Hsp90 ATPase inhibitory activity wasinvestigated by the malachite green assay. All the compounds in the studydemonstrated a moderate to potent ATPase inhibitory profile, with IC50 valuesranging from 0.18 to 6.80 μM. Compounds 4j, 4h, 4f, and 4i exhibited maximuminhibitory 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 ATPaseinhibition IC50 = 0.90 μM). Compounds 4h and 4j with IC50 values of22.82 ± 0.532, 20.78 ± 0.234 and 21.32 ± 0.765, 28.43 ± 0.653 μM showedsignificantly greater potencies against the MCF-7 and HepG2 cell lines,respectively. Compound 4j showed good antioxidant activities in the DPPH testand H2O2 assay (IC50 = 20.13.23 ± 0.32 and 23.27 ± 0.32 μg/mL) when comparedwith the standard ascorbic acid (IC50 = 19.16 ± 0.20 and 20.66 ± 1.09 μg/mL). Amolecular docking study was performed to observe the binding efficiency andsteric interactions of the lead moiety.