1. Synthesis, Structure and Cytotoxicity of N,N and N,O-Coordinated Ru II Complexes of 3-Aminobenzoate Schiff Bases against Triple-negative Breast Cancer.
- Author
-
Mukherjee A, Koley TS, Chakraborty A, Purkait K, and Mukherjee A
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Cycle Checkpoints drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Coordination Complexes chemical synthesis, Coordination Complexes chemistry, Drug Screening Assays, Antitumor, Humans, Ruthenium chemistry, Schiff Bases chemistry, Schiff Bases pharmacology, Triple Negative Breast Neoplasms pathology, Tumor Cells, Cultured, meta-Aminobenzoates chemistry, Antineoplastic Agents pharmacology, Coordination Complexes pharmacology, Ruthenium pharmacology, Triple Negative Breast Neoplasms drug therapy, meta-Aminobenzoates pharmacology
- Abstract
Half-sandwich Ru
II complexes, [(YZ)RuII (η6 -arene)(X)]+, (YZ=chelating bidentate ligand, X=halide), with N,N and N,O coordination (1-9) show significant antiproliferative activity against the metastatic triple-negative breast carcinoma (MDA-MB-231). 3-aminobenzoic acid or its methyl ester is used in all the ligands while varying the aldehyde for N,N and N,O coordination. In the N,N coordinated complex the coordinated halide(X) is varied for enhancing stability in solution (X=Cl, I). Rapid aquation and halide exchange of the pyridine analogues, 2 and 3, in solution are a major bane towards their antiproliferative activity. Presence of free -COOH group (1 and 4) make complexes hydrophilic and reduces toxicity. The imidazolyl 3-aminobenzoate based N,N coordinated 5 and 6 display better solution stability and efficient antiproliferative activity (IC50 ca. 2.3-2.5 μM) compared to the pyridine based 2 and 3 (IC50 >100 μM) or the N,O coordinated complexes (7-9) (IC50 ca. 7-10 μM). The iodido coordinated, 6, is resistant towards aquation and halide exchange. The N,O coordinated 7-9 underwent instantaneous aquation at pH 7.4 generating monoaquated complexes stable for at least 6 h. Complexes 5 and 6, bind to 9-ethylguanine (9-EtG) showing propensity to interact with DNA bases. The complexes may kill via apoptosis as displayed from the study of 8. The change in coordination mode and the aldehyde affected the solution stability, antiproliferative activity and mechanistic pathways. The N,N coordinated (5 and 6) exhibit arrest in the G2/M phase while the N,O coordinated 8 showed arrest in the G0/G1 phase., (© 2021 Wiley-VCH GmbH.)- Published
- 2021
- Full Text
- View/download PDF