ABSTRACT
Two acylhydrazone based zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) were synthesized from 3-(1-(salicyloylhydrazono)ethyl) pyridine (HL). Single crystal X-ray structure analyses showed that complexes Zn1 and Zn2 have a zero-dimensional monomer or dimer structure. Antiproliferative activity studies revealed that Zn1 and Zn2 are both more effective against A549 cells than cisplatin. The results of the reactive oxygen species (ROS) generation assay on A549 cells showed that both Zn1 and Zn2 induced apoptosis through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of Zn1 and Zn2 on A549 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. What's more, the results of wound-healing assay showed that Zn1 and Zn2 could inhibit the migration of A549 cells. Western blot analysis further demonstrated that Zn1 and Zn2 induced cell apoptosis through the mitochondrial pathway, in which process, the expression level of cytochrome C, cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 proteins increased while pro-caspase 3 and pro-caspase 9 expression decreased. In vivo anticancer evaluation demonstrated that both Zn1 and Zn2 complexes effectively inhibited tumor growth without causing significant toxicity in systemic organs.
Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Coordination Complexes , Drug Screening Assays, Antitumor , Hydrazones , Lung Neoplasms , Zinc , Animals , Mice , A549 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Dose-Response Relationship, Drug , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Zinc/chemistry , Zinc/pharmacologyABSTRACT
In the crystal structure of the title compound C(15)H(27)N(3)O(4), the mol-ecule is located on a twofold axis and the asymmetric unit contains one half-mol-ecule, with one N and one C atom lying on the rotation axis. The pyridine ring is the hydrogen-bond acceptor, while two hydroxyl O atoms act as hydrogen-bond donors in intra-molecular O-Hâ¯N and intermolecular O-Hâ¯N and O-Hâ¯O hydrogen bonds, thereby forming a closed hydrogen-bonded cage.