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

<b>Background/Objectives</b>: 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. <b>Methods</b>: In order t...

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Bibliographic Details
Main Authors: Marco Paolino, Mario Saletti, Jacopo Venditti, Arianna Zacchei, Alessandro Donati, Claudia Bonechi, Germano Giuliani, Stefania Lamponi, Andrea Cappelli
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/4/473
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Summary:<b>Background/Objectives</b>: 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. <b>Methods</b>: In order to obtain innovative crown ethers derivatives, a Morita–Baylis–Hillman adduct (MBHA) acetate (<b>4</b>) 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 (<b>5a-d</b>). These dimeric MBHA derivatives were reacted with n-butylamine to afford tunable macrocyclic crown ether-paracyclophane hybrid architectures (<b>6a-d</b>). <b>Results</b>: Compounds (<i>E</i>,<i>Z</i>)-<b>6a</b>, (<i>E</i>,<i>E</i>)-<b>6a</b>, <b>6b-d</b> showed, in human breast cancer MDA-MB-231 and human melanoma A375 cells, IC<sub>50</sub> values comparable with those of reference anticancer agent Doxorubicin. <b>Conclusions</b>: This exploration approach provides original new macrocyclic architectures potentially useful as anticancer agents.
ISSN:1424-8247