Clicking Fe metallohelices tunes cancer-cell selectivity
Copper-click derivatisation of a stable Fe2L3 helix gives Δ-[Fe2L3a3]Cl4, which is more cancer-selective than the parent, hits cancer stem cells, and still has a fully characterised coordination core.
Source
Discovery of selective, antimetastatic and anti-cancer stem cell metallohelices <i>via</i> post-assembly modification
What they did
Authors CuAAC-functionalised triplex alkynyl metallohelices, confirmed products by NMR/MS, then compared enantiomers in cancer versus non-cancer cells, wound-healing, invasion, Na+/K+ ATPase, and CD133+ colonosphere assays.
What they found
Click conversion raised ovarian/breast potency ~7–25-fold. Δ-[Fe2L3a3]Cl4 left 71% of a scratch open versus 33% control, cut invasion 58%, IC50 1.21 μM on CD133+ CSCs, and inhibited Rb+ uptake 35–47%. p53-null cells were not resistant.
The limits
What it doesn't show
These are cell-based pharmacology endpoints, not a clinical anticancer trial or a solved target co-crystal of the helix with Na+/K+ ATPase.
Key terms
- Metallohelix
- Self-assembled multimetallic helical coordination compound, here Fe2L3.
- Post-assembly modification (PAM)
- Covalent chemistry on an already-formed cage/helix, here CuAAC.
- Δ vs Λ
- Enantiomers of the helix; Δ is more cancer-selective for the clicked series.
- CuAAC
- Copper-catalysed azide–alkyne cycloaddition used to add benzyltriazoles.
- CSC
- Cancer stem cell–enriched CD133+ populations assayed as colonospheres.
Flashcards
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
Quiz yourself
PAM on these helices used:
Common questions
What reaction did PAM use?
CuAAC of alkynyl helices with benzyl azides.
Which enantiomer is more cancer-selective after clicking?
The Δ isomer of [Fe2L3a3]Cl4.
CSC IC50 on HCT116.CD133+?
1.21 ± 0.25 μM.
Does p53 loss confer resistance?
Not for the Δ-metallohelices, unlike cisplatin.
More on Coordination chemistry