# Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity

## TL;DR

Researchers created new macrocyclic structures with cytotoxic properties that could be useful as anticancer agents.

## Contribution

A novel synthesis approach combining Morita–Baylis–Hillman dimers and crown ethers to form cytotoxic macrocyclic structures.

## Key findings

- The synthesized compounds showed IC50 values comparable to doxorubicin in breast cancer and melanoma cells.
- Macrocyclic crown ether-paracyclophane hybrids were successfully formed using click-chemistry methods.

## Abstract

Background/Objectives: Crown ethers have received increasing interest owing to their ability to form stable complexes with cations. This molecular feature has been successfully exploited in the development of biologically relevant ionophores. Methods: In order to obtain innovative crown ethers derivatives, a Morita–Baylis–Hillman adduct (MBHA) acetate (4) bearing a phenylacetylene moiety was dimerized via the click-chemistry CuAAC reaction with oligo(ethylene glycol) diazide derivatives to build-up a small series of dimeric MBHA derivatives (5a-d). These dimeric MBHA derivatives were reacted with n-butylamine to afford tunable macrocyclic crown ether-paracyclophane hybrid architectures (6a-d). Results: Compounds (E,Z)-6a, (E,E)-6a, 6b-d showed, in human breast cancer MDA-MB-231 and human melanoma A375 cells, IC50 values comparable with those of reference anticancer agent Doxorubicin. Conclusions: This exploration approach provides original new macrocyclic architectures potentially useful as anticancer agents.