EPR and electrochemical interpretation of bispyrazolylacetate anchored Ni(ii) and Mn(ii) complexes: cytotoxicity and anti-proliferative activity towards human cancer cell lines. (3rd May 2018)

• Record Type: Journal Article
• Authors: Das, Kuheli; Beyene, Belete B.; Datta, Amitabha; Garribba, Eugenio; Roma-Rodrigues, Catarina; Silva, Ana; Fernandes, Alexandra R.; Hung, Chen-Hsiung
• Is Part Of: New journal of chemistry. Volume 42:Number 11(2018)
• Page Start: 9126
• Page End: 9139
• Publication Date: 2018-05-03
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c8nj01033a
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : The cytotoxicity and antiproliferative activity are carried out along with EPR and redox interpretation. Abstract : Two mononuclear Ni II and Mn II compounds, [Ni(bdtbpza )2 (CH3 OH)4 ] (1 ) and [Mn(bdtbpza )2 (CH3 OH)2 (H2 O)2 ] (2 ), are afforded by employing a 'scorpionate' type precursor [bdtbpza = bis(3, 5-di- t -butylpyrazol-1-yl)acetate]. The single crystal X-ray structure reveals that the central metal ion (Ni II for1 and Mn II for2 ) is surrounded by a pair of Oacetate atoms of two bis(pyrazol-1-yl)acetate units, while four OMeOH donors for1 and two OMeOH plus two Owater for2 complete the first coordination sphere. Thus, both compounds exhibit a slightly distorted octahedral geometry possessing an O6 coordination environment. EPR spectra of Cu II -doped1 and of2 recorded on the polycrystalline solids and in organic solution confirm the octahedral geometry around the metal ions and the binding of six oxygen atoms. The electrochemical study of compounds1 and2 shows that one electron reduction of Mn II occurs at a more negative potential than Ni II, indicating a lower tendency of reduction for Mn than Ni. Both compounds displayed a high cytotoxic activity against A2780 ovarian carcinoma cells and no cytotoxic activity in normal primary human fibroblasts for concentrations up to 55 μM. Notwithstanding, compound1 is found to be the most cytotoxic towards A2780 cancer cells. The cytotoxic activity of compound1 is correlated with the induction of apoptosis associated with a higher mitochondria dysfunction and autophagy cell death. In addition, the compounds can induce oxidative damage leading to ROS accumulation. Overall, the data presented here demonstrate that1 has potential for further in vivo studies aiming at its future application in ovarian cancer therapy.