ArticleRSC medicinal chemistry2023
Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.
Article in RSC medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Site-selective arylations of nature-inspired flavonoids or steroidal phenolsJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Article
- Advancements in targeting tumor suppressor genes (p53 and BRCA 1/2) in breast cancer therapy.Molecular diversity · 2025Review
- The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relevant pharmacological benefit gained from the hybrid coupling was further confirmed by virtual combination index calculations using the Chou method. Compound 13 modulated doxorubicin-induced DNA damage response through inhibiting the ATR-dependent activation of Chk-1, while increasing the activation of Chk-2. Our results suggest that the new hybrids may serve as new leads against triple negative breast cancer.
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Registered trials
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