Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study

• Published in: Journal of inorganic biochemistry Vol. 257; p. 112580
• Main Authors: Nandhini, S., Thiruppathi, G., Ranjani, M., Puschmann, Horst, Ravi, M., Sundararaj, P., Prabhakaran, R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; C. elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Line, Tumor; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; DNA/protein binding; FACS; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Humans; Longevity - drug effects; MDA-MB-231 Cells; MTT assay; Ruthenium - chemistry; Ruthenium - pharmacology; Ruthenium(II) complexes; DNA/protein binding; C. elegans; FACS; MTT assay; Ruthenium(II) complexes
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112580

Pincer type coumarin based N-substituted semicarbazone ligands HL1–4 and their corresponding ruthenium(II) complexes (1–4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL3 and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods. The results of In vitro cytotoxicity showed the significant cytotoxic potential of the complexes against MDA-MB-231 cells (TNBC- Triple-negative breast cancer). Among the complexes, 1 and 4 have shown appreciable results. Further, antimigratory activity against the MDA-MB-231 cells was studied for the complexes 1 and 4. The percentage cell cycle arrest, apoptosis and necrosis were explored by flow cytometry. The in vivo anti-tumor activity of the complexes 1 and 4 using C. elegans as model organism was established by using the tumoral C. elegans strain JK1466 (gld-1(q485)), which bears a mutation in the gld-1 tumor suppressor gene. We have determined the effect of our complexes on tumor gonad reduction and found to be non toxic to the JK1466 worms and they have prolonged their mean lifespan with potential antioxidant ability by overcoming stress responses. Overall, our study reported herein demonstrated that the complexes 1 and 4 could be established as potential metallo-drugs substantiating further exploration. Four ruthenium(II) complexes have been synthesized and characterized by various spectro analytical techniques. X-ray crystallographic study confirmed the molecular structure of the ligand HL3 and complex 3. The CT-DNA and BSA protein interaction of these complexes were studied by absorption and emission titrations. The cytotoxic activity was evaluated against MDA-MB-231 (human breast cancer cells). An in vivo investigation of the antitumor activity of complexes 1 and 4 in C. elegans showed the non-toxic nature of the complexes without any adverse effects on the growth and reproduction of the JK1466 worms. Ruthenium(II) complexes; C. elegans; anti-metastasis; antioxidant; Lifespan expansion. Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study [Display omitted] •Four Ru(II) complexes have been synthesized and characterized.•X-ray crystallographic study confirmed the ONO pincer type coordination of the ligand HL3 in complex 3•The interaction of the complexes with CT-DNA and BSA was explored by absorption and emission spectroscopic techniques.•The cytotoxicity was evaluated against MDA-MB-231 (human breast cancer cells).•The in vivo cytotoxicity studies of complexes 1 and 4 in c.elegans proved their non toxic nature to JK1466 worms