Fe3O4 nanoparticles mediated synthesis of novel spirooxindole ‐dihydropyrimidinone molecules as Hsp90 inhibitors

Novel spirooxindole ‐dihydropyrimidinones were synthesized by Fe3O4 nanoparticles intervened synthesis and their Hsp90 ATPase inhibitory activities were investigated. All compounds showed a moderate to potent ATPase inhibitory profile, with IC50 values ranging from 0.18 to 6.80  µM, Compounds4j,4h,4f, and4i were more active than the standard, geldanamycin. AbstractHeat 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 Fe3O4 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. Compounds4j,4h,4f, and4i 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). Compounds4h and4j 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. Compound4j showed good antioxidant activities in the DPPH test and H2O2 assay (IC50 = 20.13.23 ± 0.32 and 23.27 ± 0.32 μg/mL) when compare...

Source: Archiv der Pharmazie - November 28, 2018 Category: Drugs & Pharmacology Authors: Srinubabu Maddela, Ajitha Makula, Mario D. Galigniana, Della G. T. Parambi, Fernando Federicci, Gisela Mazaira, Omnia M. Hendawy, Sanal Dev, Githa E. Mathew, Bijo Mathew Tags: FULL PAPER Source Type: research