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Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes
Authors:Afaf Oulmidi  Smaail Radi  Abderrazak Idir  Abdelmajid Zyad  Imad Kabach  Mohamed Nhiri  Koen Robeyns  Aurelian Rotaru  Yann Garcia
Abstract:The complexes: [CoL2](ClO4)2 (1), [FeL2](ClO4)2 (2), [NiL2](ClO4)2 (3) and [MnLCl2] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L′ (diethyl 2,2′-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL′Cl2] (1′) exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1′ against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

The complexes: [CoL2](ClO4)2 (1), [FeL2](ClO4)2 (2), [NiL2](ClO4)2 (3) and [MnLCl2] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized.
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