Affiliation:
1. Department of Organic Chemistry, Faculty of Chemical Engineering and Technology University of Zagreb Zagreb Croatia
2. Centre for Applied Bioanthropology Institute for Anthropological Research Zagreb Croatia
3. Division of Materials Chemistry Ruđer Bošković Institute Zagreb Croatia
Abstract
AbstractAmong ruthenium complexes studied as anticancer metallodrugs, NKP‐1339, NAMI‐A, RM175, and RAPTA‐C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium‐based anticancer drugs and the cytostatic activity of organometallic complexes with triazole‐ and coumarin‐derived ligands, we set out to synthesize Ru(II) complexes of coumarin‐1,2,3,‐triazole hybrids (L) with the general formula [Ru(L)(p‐cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p‐cymene)(Cl)]ClO4 (2aRu) was determined by single‐crystal X‐ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC‐1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c‐Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half‐sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC‐1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin‐modified half‐sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.