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Title: Heteroleptic Platinum (II) Dithiocarbamates: Synthesis, Characterization, Anticancer, DNA Binding and DNA Denaturing Studies.
Authors: Imran, Muhammad
Keywords: Physical Sciences
Issue Date: 2020
Publisher: Quaid-i-Azam University, Islamabad.
Abstract: In the present study, 63 different neutral and cationic heteroleptic platinum(II) dithiocarbamates have been synthesized by the simultaneous addition of piperazine/ piperidine based dithiocarbamate and substituted organophosphine to the methanolic solution of Platinum(II) chloride. Various dithiocarbamates and organophosphine used were sodium 4-(2-pyrimidyl)piperazine-1-carbodithioate (L-1), sodium 4-(2- pyridyl)piperazine-1-carbodithioate (L-2), sodium 4-(3-methoxyphenyl)piperazine-1- carbodithioate (L-3), sodium 4-benzylpiperidine-1-carbodithioate (L-4), sodium 4- mehtylpiperidine-1-carbodithioate (L-5), sodium N-mehtylpiperazine-1-carbodithioate (L-6), sodium 4-(2-fluorophenyl)piperazine-1-carbodithioate (L-7), triphenylphosphine, tris(p-methoxyphenyl)phosphine, tri(p-tolyl)phosphine, tris(p-chlorophenyl)phosphine, tri(o-tolyl)phosphine, diphenyl-p-tolylphosphine, tris(2-cyanoethyl)phosphine, tri(cyclohexyl)phosphine and 1,4-bis-(diphenylphosphino)butane. The purity of complexes, binding mode of the ligand, structural confirmation, geometry assignment around metal centre and degree of axial protection were made by using various analytical techniques like elemental analysis, FT-IR, multinuclear (1 H, 13C and 31P) NMR and X-ray single crystal analysis. Additionally, DFT studies were used to confirm labile nature of chloride ligand, estimation of axial protection in the absence of crystal structure and stability of complexes by calculating energy gap between HOMO and LUMO orbitals of the complexes. However, before carrying in vitro anticancer activity, stability in different solutions and lipophilicity (linked with cellular uptake) of complexes was also calculated to check their suitability as antitumor agent. Later on complexes were screened for in vitro cytotoxic efficacy against three cancer cell lines namely, MCF-7 (human breast adenocarcinoma), LU (human lung carcinoma), Hepa-1c1c7 (mouse liver hepatoma) by using MTT assay using cisplatin as a standard drug. Moreover, selected complexes were also tested against NF-κB (Nuclear factor kappa-light chain enhancer of activated B cells) which plays a seminal role for suppression of apoptosis in cancer cells. Hence, activity against NF-κB signifies that death of the cancer cells may be due to hindering the activity of NF-κB and subsequent initiation of the apoptosis. DNA binding and denaturing studies were performed by electronic absorption spectroscopy and various binding and xxxviii thermodynamic parameters were calculated to understand the nature of interaction of synthesized complexes with target DNA. Furthermore, the mode of interaction of complexes with DNA was confirmed by viscometry.
Gov't Doc #: 20186
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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