Synthesis and evaluation of new polynuclear organometallic Ru(ii), Rh(iii) and Ir(iii) pyridyl ester complexes as in vitro antiparasitic and antitumor agents

Abstract

New polynuclear organometallic Platinum Group Metal (PGM) complexes containing di- and tripyridyl ester ligands have been synthesised and characterised using analytical and spectroscopic techniques including (1)H, (13)C NMR and infrared spectroscopy. Reaction of these polypyridyl ester ligands with either [Ru(p-cymene)Cl2]2, [Rh(C5Me5)Cl2]2 or [Ir(C5Me5)Cl2]2 dimers yielded the corresponding di- or trinuclear organometallic complexes. The polyaromatic ester ligands act as monodentate donors to each metal centre and this coordination mode was confirmed upon elucidation of the molecular structures for two of the dinuclear complexes. The di- and trinuclear PGM complexes synthesized were evaluated for inhibitory effects on the human protozoal parasites Plasmodium falciparum strain NF54 (chloroquine sensitive), Trichomonas vaginalis strain G3 and the human ovarian cancer cell lines, A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant) cell lines. All of the complexes were observed to have moderate to high antiplasmodial activities and the compounds with the best activities were evaluated for their ability to inhibit formation of synthetic hemozoin in a cell free medium. The in vitro antitumor evaluation of these complexes revealed that the trinuclear pyridyl ester complexes demonstrated moderate activities against the two tumor cell lines and were also less toxic to model non-tumorous cells.

Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes

“…In the search for drugs with improved clinical effectiveness, reduced toxicity and a broader spectrum of activity, other metals than platinum have been considered, such as Ru, Rh, Cu, Cd and Au etc. [6][7][8][9][10]. Ruthenium complexes are very promising, especially from the viewpoint of overcoming cisplatin resistance with a low general toxicity.…”

Trinuclear Half‐Sandwich RuII, RhIII and IrIII Polyester Organometallic Complexes: Synthesis and in vitro Evaluation as Antitumor Agents

“…This is ascribed to the cleavage of ester bonds by esterases, and thus polyester dendrimers exhibit lower toxicities 10. Mono‐ and polynuclear Ru II , Rh III and Ir III arene complexes of ester‐containing compounds with monodentate donor atoms have previously demonstrated pharmacological activities, which promote their development and further study 11–14. The combination of organometallic compounds with compounds of known therapeutic value is a prolific area of research, and, together with the concept of multinuclearity, is a popular strategy in drug design, which can possibly afford novel modes of action.…”

“…This study details with the synthesis and characterisation of a series of bidentate, trimeric aromatic ester organometallic complexes containing Ru II , Rh III and Ir III . The ligands contain chelating, bidentate donor atoms ( N , N ‐ and N , O ‐) in comparison to work done previously in our group where monodentate‐containing ( N ‐) trinuclear Ru II , Rh III and Ir III arene complexes were prepared 14. These organometallic complexes couple the established in vitro pharmacological activity of half‐sandwich Ru II , Rh III and Ir III complexes together with the known lipophilic nature of the ester functionalities.…”

Investigation of antibacterial activity and related mechanism of a ruthenium(II) polypyridyl complex

“…Especially in recent years, microorganisms resistant to antimicrobial agents are serious problems worldwide in the fight against infectious diseases and the development of materials with the ability to inhibit bacterial growth has been of great interest in recent years due to their potential use in everyday products like paints, kitchenware, school and hospital utensils [3]. In the search for drugs with improved clinical effectiveness, reduced toxicity and a broader spectrum of activity, other metals than platinum have been considered, such as Ru, Rh, Cu, Cd and Au [4][5][6][7][8][9]. Ruthenium complexes are very promising, especially from the viewpoint of overcoming cisplatin resistance with a low general toxicity [10][11][12][13].…”