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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2025-03-01
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| author | Marco Paolino Mario Saletti Jacopo Venditti Arianna Zacchei Alessandro Donati Claudia Bonechi Germano Giuliani Stefania Lamponi Andrea Cappelli |
| author_facet | Marco Paolino Mario Saletti Jacopo Venditti Arianna Zacchei Alessandro Donati Claudia Bonechi Germano Giuliani Stefania Lamponi Andrea Cappelli |
| author_sort | Marco Paolino |
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| description | <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. |
| format | Article |
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| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-1fbb671d3b49457798d4eb761d2d229c2025-08-20T03:13:55ZengMDPI AGPharmaceuticals1424-82472025-03-0118447310.3390/ph18040473Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable CytotoxicityMarco Paolino0Mario Saletti1Jacopo Venditti2Arianna Zacchei3Alessandro Donati4Claudia Bonechi5Germano Giuliani6Stefania Lamponi7Andrea Cappelli8Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, ItalyDipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, Italy<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.https://www.mdpi.com/1424-8247/18/4/473macrocyclic compoundscrown ethersparacyclophane derivativescytotoxicityanticancer agents |
| spellingShingle | Marco Paolino Mario Saletti Jacopo Venditti Arianna Zacchei Alessandro Donati Claudia Bonechi Germano Giuliani Stefania Lamponi Andrea Cappelli Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity Pharmaceuticals macrocyclic compounds crown ethers paracyclophane derivatives cytotoxicity anticancer agents |
| title | Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity |
| title_full | Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity |
| title_fullStr | Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity |
| title_full_unstemmed | Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity |
| title_short | Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita–Baylis–Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity |
| title_sort | synthesis and reactivity of oligo ethylene glycol tethered morita baylis hillman dimers in the formation of macrocyclic structures showing remarkable cytotoxicity |
| topic | macrocyclic compounds crown ethers paracyclophane derivatives cytotoxicity anticancer agents |
| url | https://www.mdpi.com/1424-8247/18/4/473 |
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