Journal
APPLIED ORGANOMETALLIC CHEMISTRY
Volume 35, Issue 1, Pages -Publisher
WILEY
DOI: 10.1002/aoc.6036
Keywords
dithiocarbazate; DNA fragmentation; EAC cells; extrinsic-intrinsic apoptosis pathway; nickel(II) complex
Categories
Funding
- Ministry of Science and Technology (MOST) [39.00.0000.09.02.90.18-19/27Phy's, 39.00.0000.09.06.79.2017/10ID]
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The synthesized nickel(II) complex demonstrated inhibitory effects on Ehrlich ascites carcinoma cells by regulating the expression of multiple apoptotic genes, suggesting its potential as a compound for cancer treatment. Both experimental and computational studies confirmed the compound's ability to successfully inhibit EAC cell growth, highlighting its promising role in anticancer therapy.
A novel bis[benzyl-N '-hydrazinecarbodithioato-kappa N-2 ',S]nickel(II) complex was synthesized and characterized by means of various physical, chemical, and spectroscopic techniques. The X-ray single crystal diffraction analysis indicated two independent close comparable bis-chelated square planar complexes oftrans-configuration, where S-benzyl dithiocarbazate (SBDTC) ligand is coordinated via N,S-donor set. The complex is able to inhibit Ehrlich ascites carcinoma (EAC) cell proliferation by 51.81% and 75.75%, with 0.3 and 50 mg kg(-1)(dose adjusted) dose, respectively, administered intraperitoneally for five successive days in mice model. Apoptotic cell morphological changes were examined using optical and fluorescence microscopy techniques. Expression pattern of apoptosis regulatory genes in EAC cells treated with the synthesized nickel(II) complex for five consecutive days showed an increased expression of P-53, Bax, Cas-8, Cas-9, Cas-3, Cyt-c, and TNF-alpha proapoptotic genes and decreased expression of antiapoptotic Bcl-2 gene. The Ni(II) complex and Bleomycin (standard drug) were used in molecular docking coupled with molecular dynamics simulation studies with the aim to support the experimental results and to investigate the apoptotic effect towards the targeting apoptotic genes. Both experimental and computational studies reveal that the nickel(II) complex inhibits EAC cells growth successfully, suggesting a potential compound for cancer treatment.
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