Impact of the ferrocenyl group on cytotoxicity and KSP inhibitory activity of ferrocenyl monastrol conjugates. Issue 2 (17th November 2021)

• Record Type: Journal Article
• Authors: Wieczorek-Błauż, Anna; Kowalczyk, Karolina; Błauż, Andrzej; Makal, Anna; Pawlędzio, Sylwia; Eurtivong, Chatchakorn; Arabshahi, Homayon J.; Reynisson, Jóhannes; Hartinger, Christian G.; Rychlik, Błażej; Plażuk, Damian
• Is Part Of: Dalton transactions. Volume 51:Issue 2(2021)
• Page Start: 491
• Page End: 508
• Publication Date: 2021-11-17
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d1dt03553c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Introduction of the ferrocenyl group into the monastrol scaffold improved the cytotoxic activity, and increased the kinesin-spindle-protein (KSP) inhibitory activity and its ability to generate ROS which led to increased levels of apoptotic cells. 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.