Viossat B, Morgant G, Sorenson J R J, Roch-Arveiller M, Daran J C, Greenaway F T, Nguyen Huy D
Laboratoire de Chimie Générale, Faculté de Médecine et de Pharmacie, Poitiers, France.
Ann Pharm Fr. 2002 Mar;60(2):102-14.
Copper(II) and zinc(II) chelates by some non-steroidal antiinflammatory drugs NSAIDs (niflumic acid, indomethacin) and 3,5-diisopropylsalicylic acid (DIPS) were characterized by single X-ray diffraction methods. Copper(II) complexes by these two types of chelates are binuclear compounds, with Cu(2)(DIPS)(4)L(2) or Cu(2)(AINS)(4)L(2) formula (L=axial non-NSAID ligand such as diethylether, dimethylsulfoxide DMSO). In zinc(II) complex by DIPS, the metal ion is tetrahedrally coordinated and the corresponding compound is mononuclear with Zn(DIPS)(2)(DMSO)(2) formula. These copper(II) and zinc(II) complexes were found to be more active than their parent drugs from the antiinflammatory and anticonvulsant properties. It was pointed out that the Cu(2)(DIPS)(4)L(2) complexes (L=diethylether, N,N-dimethylformamide) exhibited no rotorod toxicity when examined for anticonvulsant activity using the seizure produced by maximal electroshock, following oral administration to rats.
通过单晶X射线衍射方法对一些非甾体抗炎药（NSAIDs，尼氟酸、吲哚美辛）和3,5-二异丙基水杨酸（DIPS）与铜（II）和锌（II）形成的螯合物进行了表征。这两种类型螯合物与铜（II）形成的配合物是双核化合物，其化学式为Cu₂(DIPS)₄L₂或Cu₂(AINS)₄L₂（L = 轴向非NSAID配体，如二乙醚、二甲基亚砜DMSO）。在DIPS与锌（II）形成的配合物中，金属离子呈四面体配位，相应的化合物是单核的，化学式为Zn(DIPS)₂(DMSO)₂。从抗炎和抗惊厥特性来看，这些铜（II）和锌（II）配合物比其母体药物更具活性。有人指出，当使用最大电休克诱发的癫痫发作对大鼠口服给药来检测抗惊厥活性时，Cu₂(DIPS)₄L₂配合物（L = 二乙醚、N,N-二甲基甲酰胺）未表现出转子杆毒性。
