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

Reynisson, Jóhannes

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.

Citation

Reynisson, J., Wieczorek-Błauż, A., Kowalczyk, K., Błauż, A., Makal, A., Pawlędzio, S., Eurtivong, C., Arabshahi, H. J., Hartinger, C. G., Rychlik, B., & Plażuk, D. (2021). Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates. Dalton Transactions, 51(2), 491-508. https://doi.org/10.1039/d1dt03553c

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2021
• Online Publication Date: Nov 12, 2021
• Publication Date: Nov 17, 2021
• Publicly Available Date: May 30, 2023
• Journal: Dalton Transactions
• Print ISSN: 1477-9226
• Electronic ISSN: 1477-9234
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 51
• Issue: 2
• Pages: 491-508
• DOI: https://doi.org/10.1039/d1dt03553c
• Public URL: https://keele-repository.worktribe.com/output/421604
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2021/DT/D1DT03553C