Artykuł w czasopiśmie
Brak miniatury
Licencja
CC-BYCC-BY - Uznanie autorstwa
 

Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands

Uproszczony widok
cris.lastimport.scopus2024-02-12T20:05:44Z
dc.abstract.enIspinesib is a potent inhibitor of kinesin spindle protein (KSP), which has been identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived N,N-bidentate ligands (R)- and (S)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one and studies on their chemical and biological properties. Using the enantiomerically pure (R)- and (S)-forms of the ligand, depending on the organometallic moiety, either the SM,R or RM,S diastereomers, respectively, were observed in the molecular structures of the Ru- and Os(cym) (cym = η6-p-cymene) compounds, whereas the RM,R or SM,S diastereomers were found for the Rh- and Ir(Cp*) (Cp* = η5-pentamethylcyclopentadienyl) derivatives. However, density functional theory (DFT) calculations suggest that the energy difference between the diastereomers is very small, and therefore a mixture of both will be present in solution. The organometallics exhibited varying antiproliferative activity in a series of human cancer cell lines, with the complexes featuring the (R)-enantiomer of the ligand being more potent than the (S)-configured counterparts. Notably, the Rh and Ir complexes demonstrated high KSP inhibitory activity, even at 1 nM concentration, which was independent of the chirality of the ligand, whereas the Ru and especially the Os derivatives were much less active.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorTong, Kelvin K. H.
dc.contributor.authorBudniok, Aleksandra
dc.contributor.authorHanif, Muhammad
dc.contributor.authorLeśniewska, Barbara
dc.contributor.authorMovassaghi, Sanam
dc.contributor.authorHartinger, Christian G.
dc.contributor.authorJamieson, Stephen M. F.
dc.contributor.authorSöhnel, Tilo
dc.contributor.authorReynisson, Jóhannes
dc.contributor.authorZafar, Ayesha
dc.contributor.authorPlażuk, Damian
dc.contributor.authorŁomzik, Michał
dc.contributor.authorMakal, Anna
dc.contributor.authorRychlik, Błażej
dc.contributor.authorBłauż, Andrzej
dc.contributor.authorTchoń, Daniel
dc.date.accessioned2024-01-25T11:27:45Z
dc.date.available2024-01-25T11:27:45Z
dc.date.copyright2020-10-01
dc.date.issued2020
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number20
dc.description.versionFINAL_PUBLISHED
dc.description.volume59
dc.identifier.doi10.1021/ACS.INORGCHEM.0C00957
dc.identifier.issn0020-1669
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/112322
dc.identifier.weblinkhttp://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.0c00957
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInorganic Chemistry
dc.relation.pages14879-14890
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titleMetal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands
dc.typeJournalArticle
dspace.entity.typePublication