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Fe 3 O 4 nanoparticles mediated synthesis of novel spirooxindole‐dihydropyrimidinone molecules as Hsp90 inhibitors
Author(s) -
Maddela Srinubabu,
Makula Ajitha,
Galigniana Mario D.,
Parambi Della G. T.,
Federicci Fernando,
Mazaira Gisela,
Hendawy Omnia M.,
Dev Sanal,
Mathew Githa E.,
Mathew Bijo
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800174
Subject(s) - chemistry , ic50 , dpph , stereochemistry , isatin , ascorbic acid , moiety , nuclear chemistry , biochemistry , antioxidant , in vitro , organic chemistry , food science
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 Fe 3 O 4 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 IC 50 values ranging from 0.18 to 6.80 μM. Compounds 4j , 4h , 4f , and 4i exhibited maximum inhibitory potential with IC 50 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 IC 50 = 0.90 μM). Compounds 4h and 4j with IC 50 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 H 2 O 2 assay (IC 50 = 20.13.23 ± 0.32 and 23.27 ± 0.32 μg/mL) when compared with the standard ascorbic acid (IC 50 = 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.