Synthesis of Ethylphosphonate Curcumin Mimics: Substituents Allow Switching Between Cytotoxic and Cytoprotective Activities DOI Creative Commons
Valeria Romanucci, Rita Pagano, Solveigh C. Koeberle

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 412 - 412

Published: March 29, 2025

Curcumin is recognized for its diverse biological activities, including the ability to induce apoptosis and ferroptosis. Therefore, it represents a promising candidate development of new compounds with neuroprotective anticancer properties. In order synthesize mimics improved pharmacokinetic properties (better solubility stability than curcumin) here, we present design synthesis novel curcumin analogues named Ethylphosphonate-based (EPs), which preserve pharmacophoric features curcumin. New EP were synthesized by tyrosol- melatonin-based building blocks using an orthogonal protection approach different precursors’ OH functions good yields in few steps. Comparative screenings cytotoxic cytoprotective (curcumin was used as reference compound) carried out on all cell lines (HeLa, A375, WM266, MDA-MB-231, LX2, HDF). Assays inhibitors ferroptosis (Ferrostatin-1, Fer-1) (Quinoline-Val-Asp-difluorophenoxymethyl ketone, Q-VD), combination curcumin, suggested specific death pathway (apoptotic or ferroptotic) EPs, depending aromatic moieties contained them. Interestingly, EP4 exhibited substantial effects against various human cancer WM266) while sparing normal cells (HDFs). displayed five-times-higher toxicity triple-negative MDA-MB-231 LX2 stellate The cytotoxicity exerted involves only apoptotic mechanism, contrary exerts both ferroptotic effects. Additionally, also found be very potent inhibitor ubiquitin-activating enzyme E1, reinforcing potential this compound. Furthermore, EP2 possesses high antioxidant properties, efficiently protects ferroptosis, inhibits amyloid aggregation involved AD.

Language: Английский

Synthesis of Ethylphosphonate Curcumin Mimics: Substituents Allow Switching Between Cytotoxic and Cytoprotective Activities DOI Creative Commons
Valeria Romanucci, Rita Pagano, Solveigh C. Koeberle

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 412 - 412

Published: March 29, 2025

Curcumin is recognized for its diverse biological activities, including the ability to induce apoptosis and ferroptosis. Therefore, it represents a promising candidate development of new compounds with neuroprotective anticancer properties. In order synthesize mimics improved pharmacokinetic properties (better solubility stability than curcumin) here, we present design synthesis novel curcumin analogues named Ethylphosphonate-based (EPs), which preserve pharmacophoric features curcumin. New EP were synthesized by tyrosol- melatonin-based building blocks using an orthogonal protection approach different precursors’ OH functions good yields in few steps. Comparative screenings cytotoxic cytoprotective (curcumin was used as reference compound) carried out on all cell lines (HeLa, A375, WM266, MDA-MB-231, LX2, HDF). Assays inhibitors ferroptosis (Ferrostatin-1, Fer-1) (Quinoline-Val-Asp-difluorophenoxymethyl ketone, Q-VD), combination curcumin, suggested specific death pathway (apoptotic or ferroptotic) EPs, depending aromatic moieties contained them. Interestingly, EP4 exhibited substantial effects against various human cancer WM266) while sparing normal cells (HDFs). displayed five-times-higher toxicity triple-negative MDA-MB-231 LX2 stellate The cytotoxicity exerted involves only apoptotic mechanism, contrary exerts both ferroptotic effects. Additionally, also found be very potent inhibitor ubiquitin-activating enzyme E1, reinforcing potential this compound. Furthermore, EP2 possesses high antioxidant properties, efficiently protects ferroptosis, inhibits amyloid aggregation involved AD.

Language: Английский

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