Novel Octahedral Nickel (II) Complex with Flexible Piperazinyl Moiety Exhibits Potent Cytotoxic Effect Along with Anti‐Migratory and Anti‐Metastatic Effect on Human Cancer Cells

• Published in: ChemMedChem 2024-09, Vol.19 (17), p.e202300728-n/a
• Main Authors: Mandal, Bikramaditya, Pramanik, Anik, Sarkar, Debanjan, Haldar, Anwesha, Das, Dona, Saha, Rajat, Mandal, Debdas, Bhattacharyya, Sankar
• Format: Article
• Language: English
• Subjects: Antitumor agents; Apoptosis; Breast carcinoma; Cancer; Cell death; Chelation; Conformation; Coordination compounds; Cytotoxicity; Flexible tri-dentate ligand Mixed ligand Ni(II) complex; Ligands; Lung cancer; Lung carcinoma; Malignancy; Metal complexes; Metal-organic frameworks; Metastases; Metastasis; Migration; Nickel; Nitrates; Pathogenesis; Phenols; Piperazine; Single crystals; Transition metal compounds; Tumor cell lines; Visible spectrum
• ISSN: 1860-7179; 1860-7187; 1860-7187
• DOI: 10.1002/cmdc.202300728

Synthesis of non‐platinum transition metal complexes with N,O donor chelating ligand for application against pathogenesis of cancer with higher efficacy and selectivity is currently an important field of research. We assessed the anti‐cancer effect of a mixed ligand Ni(II) complex on human breast and lung cancer cell lines in this investigation. Mononuclear mixed ligand octahedral Ni(II) complex [NiIIL(NO3)(MeOH)] complex (1), with tri‐dentate phenol‐based ligand 2,4‐dichloro‐6‐((4‐methylpiperazin‐1‐yl) methyl) phenol (HL) along with methanol and nitrate as ancillary ligand was prepared. Piperazine moiety of the ligand exists as boat conformation in this complex as revealed from single crystal X‐ray study. UV–visible spectrum of complex (1) exhibits three distinct d‐d bands due to spin‐allowed 3 A2 g→3T1 g (P), 3 A2 g→3T1 g(F) and 3 A2 g→3T2 g(F) transitions as expected in an octahedral d8 system. Our study revealed that Complex (1) induces apoptotic cell death in mouse and human cancer cells such as mcf‐7, A549 and MDA‐MB‐231 through transactivation of p53 and its pro‐apoptotic downstream targets in a dose dependent manner. Furthermore, complex (1) was able to slow the migratory rate of MDA‐MB‐231 cells′ in vitro as well as epithelia ‐mesenchymal transition (EMT), the key step for metastatic transition and malignancy. Over all our results suggest complex (1) as a potential agent in anti‐tumor treatment regimen showing both cytotoxic and anti‐metastatic activity against malignant neoplasia. A novel mononuclear mixed ligand Ni(II) complex was synthesised and fully charecterized. Evaluation of biological activity of the complex revealed low toxicity against normal cells but strong apotosis induction in human cancer cells, predominantly through p53 dependent manner while showing anti migratory, anti metastatic effect on invasive brest cancer cells.