Since the discovery of cisplatin in 1969, the research and application of platinum-based antitumor drugs has opened up a new field [1]. It has been found that the platinum-based complexes can effectively bind to DNA and inhibit the DNA replication of cancer cells to achieve the purpose of inhibiting the proliferation of cancer cells [2]. However, it is difficult to overcome the disadvantages of resistance and side effects of platinum-based drugs, the development of potential new drug molecules, in particular new non-platinum metal drugs with low-cost and lower side effects, beyond the limitation of traditional platinum drugs has become a research hotspot [3], [4].

In the past two decades, the design and synthesis of metal complexes have been widely used in the medical field. Metal complexes may act by inhibiting enzyme activities, interacting with biomolecules, enhancing lipophilicity, and changing the function of cell membrane [5], [6], [7]. Zinc complexes should not be neglected in the search for anticancer metal drug substitutes of platinum derivatives. As the second largest micronutrient of the human body, zinc is extremely important for normal functioning [8], [9]. Associated with its chemical properties, especially its absence of redox activity, zinc derivatives are ubiquitous in thousands of proteins and enzymes, it also has the ability to support different categories of coordination structures and facilitate ligand exchange. Like other micronutrient, the breakdown of the zinc balance in the body can lead to a variety of diseases and in some cases may be linked to cancer. Zinc deficiency can suppress immune function due to its pivotal role in the immune system, including cell proliferation and synthesis of RNA and DNA essential for T lymphocyte development [10], [11], [12], [13]. Apart from its physiological effects, zinc also exhibits therapeutic and preventive effects against infectious diseases. Zinc complexes have been considered as potential antitumor drugs with lower toxicity and fewer side effects compared to other metal-based drugs [4], [12], [14].

Schiff bases are usually condensed from amino and reactive carbon groups with specific physiological activities, biological characteristics of antibacterial, antioxidant and antitumor, and has been widely used in the field of biomedicine [3], [15], [16], [17], [18], [19]. Acylhydrazone compounds are a kind of special Schiff base compounds with wide applications. They can bind with some substances in the organism by intermolecular hydrogen bond, which can inhibit many physiological and chemical processes in the organism and show strong biological activity, such as antibacterial, anticancer, antiviral, anti-inflammatory, and antituberculosis, has the widespread application in the medicine aspect [20], [21], [22], [23], [24], [25], [26], [27]. Some acylhydrazone complexes have been reported to be used as antitumor agents [28], [29], [30]. However, the development of new metal-based drugs still has a long way to go and action pharmacological mechanism in vivo deserves further research.

Herein, two zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) with an acylhydrazone Schiff base 3-(1-(salicyloylhydrazono)ethyl)pyridine ligand (HL) were synthesized and characterized with single crystal X-ray crystallography, PXRD, 1HNMR, MS, UV–visible spectrum and thermogravimetric analysis (Scheme 1). The antitumor proliferation activity of the two zinc complexes was preliminarily screened using the CCK-8 kit. Subsequently, a series of cell function experiments were performed with the two zinc complexes, including scratch experiments to assess their influence on cancer cell migration, and apoptosis, ROS generation, cycle detection, and protein blotting to investigate their apoptosis mechanism. Finally, to evaluate the antitumor effect in vivo and evaluate the toxicity to various organs, we established a BALB/c nude mice model containing human lung cancer A549 cells.