Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives

The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(<i&g...

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Autores principales:	Radoslaw Kitel, Anna Byczek-Wyrostek, Katarzyna Hopko, Anna Kasprzycka, Krzysztof Walczak
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antiproliferative activity apoptosis furan-2(5<i>H</i>)-one bioisosteres silyl ethers Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/2e9510c367bf467eb0f61b2b60ff04f6
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spelling	oai:doaj.org-article:2e9510c367bf467eb0f61b2b60ff04f62021-11-25T18:39:10ZEffect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives10.3390/ph141110791424-8247https://doaj.org/article/2e9510c367bf467eb0f61b2b60ff04f62021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1079https://doaj.org/toc/1424-8247The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(<i>5H</i>)-one core. We describe a comprehensive characterization of obtained compounds with respect to their anticancer potency and selectivity towards cancer cells. All four novel compounds exert stronger antiproliferative activity than MBA. Moreover, <b>3b</b> induce apoptosis in colon cancer cell lines. A detailed investigation of the mechanism of action revealed that <b>3b</b> activity stems from the down-regulation of survivin and the activation of caspase-3. Furthermore, compound <b>3b</b> attenuates the clonogenic potential of HCT-116 cells. Interestingly, we also found that depending on the type of the silyl group, compound selectivity towards cancer cells could be precisely controlled. Collectively, we demonstrated the utility of silyl groups for adjusting both the potency and selectivity of silicon-containing compounds. These data reveal a link between the types of silyl group and compound potency, which could have bearings for the design of novel silicon-based anticancer drugs.Radoslaw KitelAnna Byczek-WyrostekKatarzyna HopkoAnna KasprzyckaKrzysztof WalczakMDPI AGarticleantiproliferative activityapoptosisfuran-2(5<i>H</i>)-onebioisosteressilyl ethersMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1079, p 1079 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antiproliferative activity apoptosis furan-2(5<i>H</i>)-one bioisosteres silyl ethers Medicine R Pharmacy and materia medica RS1-441
spellingShingle	antiproliferative activity apoptosis furan-2(5<i>H</i>)-one bioisosteres silyl ethers Medicine R Pharmacy and materia medica RS1-441 Radoslaw Kitel Anna Byczek-Wyrostek Katarzyna Hopko Anna Kasprzycka Krzysztof Walczak Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
description	The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(<i>5H</i>)-one core. We describe a comprehensive characterization of obtained compounds with respect to their anticancer potency and selectivity towards cancer cells. All four novel compounds exert stronger antiproliferative activity than MBA. Moreover, <b>3b</b> induce apoptosis in colon cancer cell lines. A detailed investigation of the mechanism of action revealed that <b>3b</b> activity stems from the down-regulation of survivin and the activation of caspase-3. Furthermore, compound <b>3b</b> attenuates the clonogenic potential of HCT-116 cells. Interestingly, we also found that depending on the type of the silyl group, compound selectivity towards cancer cells could be precisely controlled. Collectively, we demonstrated the utility of silyl groups for adjusting both the potency and selectivity of silicon-containing compounds. These data reveal a link between the types of silyl group and compound potency, which could have bearings for the design of novel silicon-based anticancer drugs.
format	article
author	Radoslaw Kitel Anna Byczek-Wyrostek Katarzyna Hopko Anna Kasprzycka Krzysztof Walczak
author_facet	Radoslaw Kitel Anna Byczek-Wyrostek Katarzyna Hopko Anna Kasprzycka Krzysztof Walczak
author_sort	Radoslaw Kitel
title	Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
title_short	Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
title_full	Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
title_fullStr	Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
title_full_unstemmed	Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives
title_sort	effect of selected silyl groups on the anticancer activity of 3,4-dibromo-5-hydroxy-furan-2(5<i>h</i>)-one derivatives
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2e9510c367bf467eb0f61b2b60ff04f6
work_keys_str_mv	AT radoslawkitel effectofselectedsilylgroupsontheanticanceractivityof34dibromo5hydroxyfuran25ihionederivatives AT annabyczekwyrostek effectofselectedsilylgroupsontheanticanceractivityof34dibromo5hydroxyfuran25ihionederivatives AT katarzynahopko effectofselectedsilylgroupsontheanticanceractivityof34dibromo5hydroxyfuran25ihionederivatives AT annakasprzycka effectofselectedsilylgroupsontheanticanceractivityof34dibromo5hydroxyfuran25ihionederivatives AT krzysztofwalczak effectofselectedsilylgroupsontheanticanceractivityof34dibromo5hydroxyfuran25ihionederivatives
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Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5<i>H</i>)-One Derivatives

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