Successful introduction of cytotoxic cisplatin and related platinum complexes in clinical practice initiated research into antitumor properties of organometallic and coordination complexes. Ruthenium complexes belong to the most promising antitumor drug candidates. For example, half-sandwich Ru(II) arene complexes such as RAPTA-T ([Ru(η⁶-C₆H₅Me)Cl₂(pta)]) and RAPTA-C ([Ru(η⁶-p-cymene)Cl₂(pta)] (where pta = 1,3,5-triaza-7-phosphaadamantane) have been developed and thoroughly investigated. RAPTA-T exhibits remarkable selectivity against metastatic tumors in vivo [1], whereas RAPTA-C also shows promising angiostatic activity [2]. In contrast to widely studied half-sandwich ruthenium η⁶-arene complexes, stabile 18-electron cationic full-sandwich ruthenium complexes of the general formula ([Ru(η⁶-arene)(η⁵-Cp*)]+A- (where Cp* is pentamethylcyclopentadienyl and A- represents an uncoordinated anion) received less attention. An interesting cytotoxic activity has been reported for some of them [3-5], but antimetastatic activity of these cationic complexes has not been investigated.
We have prepared a series of Ru(II) complexes of the general formula [Ru(η⁶-arene)(η⁵-Cp*)]+ Cl−, where the arene ligand is the phenyl moiety of benzyl hexopyranosides or benzyl ether-protected hexopyranoses. These complexes had negligible cytotoxicity, but some of them, in particular complex (1), showed anti-migratory and anti-invasive effects in vitro comparable to those of the reference compounds RAPTA-C and RAPTA-T.
Furthermore, we have also prepared Ru(II) complexes with carbohydrate-substituted chelate tetrazene ligand. These tetrazene complexes had variable cytotoxicity. The most active was complex (2), which exhibited cytotoxicity in low micromolar range.
Financial Support of the Czech Science Foundation is gratefully acknowledged (Project GA 17-05838S)
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