Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates

Anna Wieczorek-Błauż; Karolina Kowalczyk; Andrzej Błauż; Anna Makal; Sylwia Pawlȩdzio; Chatchakorn Eurtivong; Homayon J. Arabshahi; Jóhannes Reynisson; Christian G. Hartinger; Błażej Rychlik; Damian Plażuk

doi:10.1039/d1dt03553c

Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates

Anna Wieczorek-Błauż, Karolina Kowalczyk, Andrzej Błauż, Anna Makal, Sylwia Pawlȩdzio, Chatchakorn Eurtivong, Homayon J. Arabshahi, Jóhannes Reynisson, Christian G. Hartinger, Błażej Rychlik, Damian Plażuk

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol-the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity towards a panel of sensitive and ABC-overexpressing cancer cells. Most cytotoxic compounds exhibited also higher KSP modulatory activity and ability for ROS generation compared to monastrol. The increased bioactivity of the studied compounds can be attributed to the presence of the ferrocenyl group.

Original language	English
Pages (from-to)	491-508
Number of pages	18
Journal	Dalton Transactions
Volume	51
Issue number	2
DOIs	https://doi.org/10.1039/d1dt03553c
State	Published - Jan 14 2022
Externally published	Yes

Funding

This study was financially supported by the National Science Centre Poland (NCN) based on decision UMO-2015/17/B/ST5/ 02331.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/d1dt03553c

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title = "Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates",

abstract = "The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol-the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity towards a panel of sensitive and ABC-overexpressing cancer cells. Most cytotoxic compounds exhibited also higher KSP modulatory activity and ability for ROS generation compared to monastrol. The increased bioactivity of the studied compounds can be attributed to the presence of the ferrocenyl group.",

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doi = "10.1039/d1dt03553c",

language = "English",

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T1 - Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates

AU - Wieczorek-Błauż, Anna

AU - Kowalczyk, Karolina

AU - Błauż, Andrzej

AU - Makal, Anna

AU - Pawlȩdzio, Sylwia

AU - Eurtivong, Chatchakorn

AU - Arabshahi, Homayon J.

AU - Reynisson, Jóhannes

AU - Hartinger, Christian G.

AU - Rychlik, Błażej

AU - Plażuk, Damian

PY - 2022/1/14

Y1 - 2022/1/14

N2 - The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol-the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity towards a panel of sensitive and ABC-overexpressing cancer cells. Most cytotoxic compounds exhibited also higher KSP modulatory activity and ability for ROS generation compared to monastrol. The increased bioactivity of the studied compounds can be attributed to the presence of the ferrocenyl group.

AB - The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol-the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity towards a panel of sensitive and ABC-overexpressing cancer cells. Most cytotoxic compounds exhibited also higher KSP modulatory activity and ability for ROS generation compared to monastrol. The increased bioactivity of the studied compounds can be attributed to the presence of the ferrocenyl group.

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ER -

Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates

Abstract

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UN SDGs

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