Martini Nancy, Parente Juliana E, Toledo Maria Eugenia, Escudero Graciela E, Laino Carlos H, Martínez Medina Juan José, Echeverría Gustavo A, Piro Oscar E, Lezama Luis, Williams Patricia A M, Ferrer Evelina G
Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP), Departamento de Química-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Boulevard 120 entre 60 y 64, C.C.962-(B1900AVV)-1900 La Plata, Argentina.
Instituto de Biotecnología del CENIIT-UNLaR (Centro de Investigación e Innovación Tecnológica), Av Luis Vernet y Apostol Felipe, 5300, La Rioja, Argentina.
J Inorg Biochem. 2017 Sep;174:76-89. doi: 10.1016/j.jinorgbio.2017.05.012. Epub 2017 Jun 1.
In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerHCl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH)[CuCl]·½HO and (SerH)[CuCl], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P2 space group with a=8.0807(2) Å, b=36.2781(8) Å, c=12.6576(3) Å, β=95.665(2)°, and Z=4 molecules per unit cell and the un-hydrate in P2 with a=13.8727(6) Å, b=7.5090(3) Å, c=18.618(1) Å, β=104.563(6)°, and Z=2. It has been suggested that Cu(II) ions might be critical in the development of mood disorders, showed potent biocidal activity, and also acted as analgesic adjuvant. To improve sertraline efficiency, the antidepressant and analgesic activities of the complex have been assessed in rats denoting a marked synergistic effect. Antithyroid and antimicrobial activities were also evaluated. Because depressive disorders and hyperthyroidism diseases led to an oxidative stress state, antioxidant capability has also been tested. The complex behaved as a good superoxide radical scavenger (IC=6.3×10M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudo-first order constant of k=0.157±0.007min has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a K of 2.90×10M showing an improvement in the uptake of sertraline by albumin at 8h incubation (time required for effective interaction of sertraline with the protein).
在当前研究中,铜配合物发挥多种生物活性的能力与舍曲林(盐酸舍曲林,一种抗抑郁药物)的药理作用相结合。合成了四氯铜酸盐(II)盐的水合形式和无水形式,即(SerH)[CuCl]·½H₂O和(SerH)[CuCl],并通过物理化学方法对其进行了表征。通过X射线衍射方法确定了晶体结构。水合配合物在单斜P2空间群中结晶,a = 8.0807(2) Å,b = 36.2781(8) Å,c = 12.6576(3) Å,β = 95.665(2)°,单位晶胞中有Z = 4个分子;无水合物在P2中,a = 13.8727(6) Å,b = 7.5090(3) Å,c = 18.618(1) Å,β = 104.563(6)°,Z = 2。有人提出铜(II)离子可能在情绪障碍的发展中起关键作用,具有强大的杀菌活性,还可作为镇痛佐剂。为提高舍曲林的疗效,已在大鼠中评估了该配合物的抗抑郁和镇痛活性,结果表明有显著的协同作用。还评估了其抗甲状腺和抗菌活性。由于抑郁症和甲状腺功能亢进疾病会导致氧化应激状态,因此也测试了其抗氧化能力。该配合物表现为良好的超氧自由基清除剂(IC₅₀ = 6.3×10⁻⁵M)。评估了该配合物作为溴过氧化物酶模拟物的能力。已确定伪一级常数k = 0.157±0.007 min⁻¹。该配合物显示出有前景的生物药理活性,白蛋白结合研究表明K为2.90×10⁻⁵M,表明在8小时孵育(舍曲林与蛋白质有效相互作用所需的时间)时白蛋白对舍曲林的摄取有所改善。