Design concepts of half-sandwich organoruthenium anticancer agents based on bidentate bioactive ligands

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules

“…Half-sandwich organometallic compounds are among the most widely studied anticancer complexes of platinum group metals such as Ru, Rh, Os, and Ir [1,2]. The physicochemical and biological properties of the half-sandwich complexes can be fine-tuned by varying the metal center, the π-bound ligand (usually arene or cyclopentadienyl derivative ring) and the facial ligands occupying the remaining coordination sites [1][2][3][4].…”

“…Half-sandwich organometallic compounds are among the most widely studied anticancer complexes of platinum group metals such as Ru, Rh, Os, and Ir [1,2]. The physicochemical and biological properties of the half-sandwich complexes can be fine-tuned by varying the metal center, the π-bound ligand (usually arene or cyclopentadienyl derivative ring) and the facial ligands occupying the remaining coordination sites [1][2][3][4]. The pianostool complexes often contain a bidentate ligand and a chlorido co-ligand as leaving group, and these components affect the solution stability, lipophilicity, the overall charge and the reactivity of the complexes; thus, they also have a strong influence on the anticancer properties [1][2][3][4][5][6][7][8].…”

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

“…During recent decades, organometallic anticancer agents have emerged [4][5][6][7] as potential pharmaceutical options. More specifically, ruthenium compounds are considered the most promising drug candidates to date, because of their favorable kinetic properties, rich redox chemistry and high selectivity for cancer cells [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In fact, several ruthenium complexes, such as the octahedral NAMI-A [23] or sodium trans-tetra-chloridobis(1Hindazole)ruthenate(III) (IT-139) [15,[24][25][26] complexes as well as arene-Ru(II) derivatives of the RAPTA family [27][28][29][30], containing the PTA ligand, or RM175 [31,32], have been complexes, such as the octahedral NAMI-A [23] or sodium trans-tetra-chloridobis(1Hdazole)ruthenate(III) (IT-139) [15,[24][25][26] complexes as well as arene-Ru(II) derivatives the RAPTA family [27][28][29][30], containing the PTA ligand, or RM175 [31,32], have been ev uated as chemotherapeutic agents in clinical trials (see Figure 1).…”

“…An interesting approach to address the problem of the resistance in the field of metallic chemotherapeutic agents is to use multi-targeted drugs. This may be achieved by linking bioactive ligands to the metal fragments [10,22,44,45]. The compounds thus obtained offer additional advantages over classic anti-cancer agents, such as improved pharmacological properties, tunable antitumor activity, intramolecular combination therapy and selective targeted properties [46].…”

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand

“…Metals play various roles in biological processes ( Buccella et al, 2019 ), e.g., proteins often use metal centers to adopt certain structures or as catalytically active sites ( Haas and Franz, 2009 ; Wodrich and Hu, 2017 ; Ghosh et al, 2021 ). Metal complexes, most often platinum compounds, have been used for a long time to treat cancer ( Jakupec et al, 2008 ; Kenny and Marmion, 2019 ; Simpson et al, 2019 ; Boros et al, 2020 ; Tremlett et al, 2021 ). In addition to the clinically successful DNA-targeting cis-, carbo- and oxaliplatin ( Johnstone et al, 2014 ), other mononuclear species studied include Ru, Os, Rh and Ir-based compounds ( Sava et al, 2003 ; Arango et al, 2004 ; Hartinger et al, 2008 ; Geldmacher et al, 2012 ; Maillet et al, 2013 ).…”