New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents

Abstract

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones. Moreover, cationic complexes containing two lonidamine-based ligands were obtained. Antiproliferative activity was studied in vitro by MTT assays. It was shown that the increase in the stability in ligand exchange reactions does not influence cytotoxicity. At the same time, the introduction of the second lonidamine fragment approximately doubles the cytotoxicity of studied complexes. The ability to induce apoptosis and caspase activation in tumour cell MCF7 was studied by employing flow cytometry.

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

“…However, the literature is rich in experimental data obtained in the study of the antitumor properties of lonidamine derivatives. The introduction of the lonidamine motif to the structure of organometallic ruthenium led to a significant increase in cytotoxic properties in relation to the MCF 7 cell line, mediated by the activation of apoptotic caspases [564]. Additionally, the combination of cisplatin, tegafur, and lonidamine in one molecule demonstrated excellent cytotoxic properties on the triple-negative breast cancer cell line due to DNA damage and the disruption of the metabolic state of cells [565].…”

Complexes of Ruthenium(II) as Promising Dual-Active Agents against Cancer and Viral Infections

“…Ru complexes represent an important class of metallo-organic compounds with numerous applications, and they are currently used in the fields of catalysis [20][21][22][23], including homogeneous, heterogeneous, and photocatalysis [24]. Moreover, numerous biological activities, such as antifungal [25], antibacterial [26], and anticarcinogenic [27][28][29][30][31][32], have been described for the complexes of Ru, as well as their uses in neurodegenerative diseases [33]. Several complexes with Ru(II) have been reported, including those with benzoic acid and their analogues [34], naphthoquinones, flavonoids, curcumins [35], N-heterocyclic carbenes (NHCs) [36], polypyridyl [37], phenanthroline [38], thiazole [39], Schiff bases [40][41][42][43], and half-sandwiched arene complexes [44].…”