Oulmidi Afaf, Radi Smaail, Idir Abderrazak, Zyad Abdelmajid, Kabach Imad, Nhiri Mohamed, Robeyns Koen, Rotaru Aurelian, Garcia Yann
LCAE, Department of Chemistry, Faculty of Sciences, University Mohamed I BP 524 60 000 Oujda Morocco
Institute of Condensed Matter and Nanosciences, Molecular Chemistry, Materials and Catalysis (IMCN/MOST), Université catholique de Louvain Belgium.
RSC Adv. 2021 Oct 27;11(55):34742-34753. doi: 10.1039/d1ra05918a. eCollection 2021 Oct 25.
The complexes: CoL (1), FeL (2), NiL (3) and [MnLCl] (4), with L = diethyl-1,1'-(pyridine-2,6-diyl)bis(5-methyl-1-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 antitumor activity of L and L' (diethyl 2,2'-(pyridine-2,6-diylbis(5-methyl-1-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'Cl] (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 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.
CoL (1)、FeL (2)、NiL (3) 和 [MnLCl] (4)，其中 L = 二乙基-1,1'-(吡啶-2,6-二基)双(5-甲基-1-吡唑-3-羧酸酯)，已合成并进行了全面表征。结构分析揭示了受抗衡离子影响的两种不同模式，其中 L 作为三齿螯合配体。通过测量 L 和 L'（二乙基 2,2'-(吡啶-2,6-二基双(5-甲基-1-吡唑-3,1-二基))二乙酸酯）及其金属配合物对血癌肥大细胞瘤细胞系 P815 的细胞生长抑制和细胞毒性特性，测试了它们的抗肿瘤活性。我们还研究了它们与抗氧化酶系统的相互作用。结果，与参考顺铂相比，[MnL'Cl] (1') 表现出最强的活性，对正常细胞 PBMCs（外周血单核细胞）无细胞毒性。另一方面，抗氧化酶活性表明金属配合物 1' 对 P815 肿瘤细胞的作用效率是超氧化物歧化酶（SOD）活性升高和过氧化氢酶（CAT）活性受到抑制。这项概念验证研究揭示了癌症治疗中的一类新分子。
