ArticleFrontiers in oncology2022
Discovery of spirooxindole-derived small-molecule compounds as novel HDAC/MDM2 dual inhibitors and investigation of their anticancer activity.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Recent advances of azomethine ylides for the synthesis of natural and synthetic bioactive pyrrolidines and spiropyrrolidines.RSC advances · 2026Review
- "Spiro-pyrrolizidine-benzyloxy hybrid as synergistic partner to doxorubicin cardio-safe breast cancer chemotherapy".Future medicinal chemistry · 2025Article
- Recent advances in the halogenated spirooxindoles as novel anticancer scaffolds: chemistry and bioactivity approach.RSC advances · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Down-regulation of histone deacetylase 7 reduces biological activities of retinal microvascular endothelial cells under high glucose condition and related mechanism.International journal of ophthalmology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simultaneous inhibition of more than one target is considered to be a novel strategy in cancer therapy. Owing to the importance of histone deacetylases (HDACs) and p53-murine double minute 2 (MDM2) interaction in tumor development and their synergistic effects, a series of MDM2/HDAC bifunctional small-molecule inhibitors were rationally designed and synthesized by incorporating an HDAC pharmacophore into spirooxindole skeletons. These compounds exhibited good inhibitory activities against both targets. In particular, compound 11b was demonstrated to be most potent for MDM2 and HDAC, reaching the enzyme inhibition of 68% and 79%, respectively. Compound 11b also showed efficient antiproliferative activity towards MCF-7 cells with better potency than the reference drug SAHA and Nutlin-3. Furthermore, western blot analysis revealed that compound 11b increased the expression of p53 and Ac-H4 in MCF-7 cells in a dose-dependent manner. Our results indicate that dual inhibition of HDAC and MDM2 may provide a novel and efficient strategy for the discovery of antitumor drug in the future.
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