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[M(arene)(HQ)Cl] complexes (M = Ru II /Os II /Rh III /Ir III ; HQ = 8-hydroxyquinoline) have shown promise as anticancer agents. To assess the effect of conjugating biotin (vitamin B7) to such compounds and improve their tumor-targeting ability through interaction with the sodium-dependent multivitamin transporter (SMVT), the chlorido co-ligand was exchanged with biotinylated 6-aminoindazole. The complexes were characterized by NMR spectroscopy and mass spectrometry, and purity was determined by elemental analysis. The compounds were shown to be stable in aqueous solution but reacted in particular with biologically relevant nitrogen-donor ligands. The biotinylated organometallics were shown to be able to interact with the high-affinity biotin-binding protein streptavidin using molecular modelling. High antiproliferative activity of the biotinylated Rh complex (IC 50 = 1.1-10 μM) and its chlorido precursor (IC 50 = 2.1-7.0 μM) was demonstrated in human HCT116, NCI-H460, COLO 205, SW620, A2780 and A2780cis cancer cells, which feature differing levels of SMVT expression. While there was no clear relationship between the anticancer activity in cells and SMVT expression, the complexes showed similar activity in cisplatin-sensitive and -resistant cells. The most potent was the biotinylated Rh derivative which displayed low toxicity toward zebrafish embryos with >75% survival up to day 4 and after treatment with up to 32 μM complex.

Kinesin-5 inhibitors offer cancer cell-targeted approach, thus securing reduced systemic toxicity compared to other antimitotic agents. By modifying the 1,4-dihydropyridine-based kinesin-5 inhibitor CPUYL064 with a ferrocenyl moiety (Fc), we designed and prepared a series of organometallic hybrids that show high antiproliferative activity, with the best compounds exhibiting up to 19-fold increased activity. This enhanced activity can be attributed to the presence of the ferrocenyl moiety.

Antimitotic agents are among the most important drugs used in anticancer therapy. Kinesin spindle protein (KSP) was proposed as a promising target for new antimitotic drugs. Herein, we report the synthesis of Ru, Os, Rh, and Ir half-sandwich complexes with the KSP inhibitor ispinesib and its ( S )-enantiomer. Conjugation of the organometallic moiety with ispinesib and its ( S )-enantiomer resulted in a significantly increased cytotoxicity of up to 5.6-fold compared to the parent compounds, with IC 50 values in the nanomolar range. The most active derivatives were the ispinesib Ru and Rh conjugates which were able to generate reactive oxygen species (ROS), which may at least partially explain their high cytotoxicity. At the same time, the Os and Ir derivatives acted as KSP inhibitors with no effects on ROS generation.

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.

Correction for 'Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines' by Karolina Kowalczyk et al., Dalton Trans., 2017, 46, 17041-17052.

A series of ferrocenyl and ruthenocenyl conjugates with colchicine bearing a 1,2,3-triazole moiety were synthesized and their anticancer properties were evaluated. We found that the most potent metallocenyl derivatives Rc4 and Rc5 are 6-7 times more cytotoxic toward HepG2 cells, while Fc4 and Fc5 are two times more cytotoxic toward HCT116 cells as colchicine. We also found that compounds Fc4, Fc5, Rc1 and Rc3-Rc5 are able to induce apoptosis, while compound Fc2 arrests mitosis.

Three types, esters, amides and 1,2,3-triazoles, of ferrocenyl-podophyllotoxin conjugates were synthesised, and their anticancer activity was evaluated. We observed that the most potent ferrocenyl derivatives were esters. Esters 15, 16 and 17 acted in a similar way to podophyllotoxin, i.e. reduced the number of G1 phase cells and induced G2/M blockage, while esters 14 and 18 and amide 19 blocked cells in S phase in a similar manner to etoposide.