Synthesis of bis[benzyl‐N′‐hydrazinecarbodithioato‐κ2 N′,S]nickel(II) complex as a novel lead molecule for cancer treatment

Ronok Zahan, Sinthyia Ahmed, Tahmida Sharmin, Mohammad A. Halim, Md. Sifat Rahi, Md. Chanmiya Sheikh, Ryuta Miyatake, Ennio Zangrando, Tarannum Naz, Md. Al‐Amin‐Al‐Azadul Islam, Md Abu Reza

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3 Citations (Scopus)

Abstract

A novel bis[benzyl-N′-hydrazinecarbodithioato-κ2 N′,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 of trans-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 P53, Bax, Cas-8, Cas-9, Cas-3, Cyt-c, and TNF-α 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.
Original languageEnglish
Article numbere6036
Pages (from-to)1-17
Number of pages17
JournalApplied Organometallic Chemistry
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

Keywords

  • dithiocarbazate
  • DNA fragmentation
  • EAC cells
  • extrinsic–intrinsic apoptosis pathway
  • nickel(II) complex

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