Oral cancer is a particularly serious oral disease. It occurs in the tongue, lips, cheeks, and floor of the mouth. Oral squamous cell carcinoma (OSCC) accounts for >90% of all oral cancer types, and the 5-year survival rate is only 40%–60% [1,2]. Although its incidence rate is low, it seriously affects the quality of life of patients. The treatment of oral cancer is mainly based on surgery, supplemented by radiotherapy and chemotherapy. Because of the unique structural characteristics of the oral cavity, postoperative reconstruction is difficult, which usually leads to poor postoperative quality of life for patients [[3], [4], [5]]. Moreover, there are currently no specific drugs available for the treatment of OSCC.

In the clinical treatment of cancer, both classical chemotherapy drugs and targeted drugs may be very effective initially, but most of them have a single pathway to kill cancer and are prone to drug resistance during the treatment process [[6], [7], [8]]. Drug combinations can help avoid resistance, but the number of possible drug combinations far exceeds the number of those tested in clinical trials [9]. Thus, multiple targets and multiple mechanisms to kill tumor cells may be reliable options for delaying or overcoming drug resistance problems [10,11]. Therefore, the development of novel antitumor drugs with high anticancer activity and multiple mechanisms is a very interesting area of research.

Studies have shown that many organotin complexes have extremely strong and broad anticancer activity superior to the anticancer activity of platinum-based anticancer drugs widely used in clinical practice in vitro [[12], [13], [14], [15]]. Thus, organotin complexes are classified as highly potent anticancer drugs with great potential for development. Among them, organotin (IV) complexes play a crucial role in the development of anticancer drugs [16]. This is attributed to two reasons: 1) The organotin (IV) complexes exhibited the highest level of cytotoxic activity [17] and were effective against various types of cancer cell lines [[18], [19], [20]]. 2) The physicochemical properties of organotin(IV) complexes and their ability to form stable complexes [21]. In addition, the anticancer activity of organotin complexes are not only related to the type and number of hydrocarbon groups attached to the tin atom, but also closely related to the ligands [22]. Meanwhile, salen-like ligands and their complexes are important in coordination chemistry because of their simple preparation and structural diversity. Therefore, they have important applications in the fields of catalytic reaction activity, photochemistry, molecular recognition, and biological activities [[23], [24], [25]].

Here, a series of novel dibutyltin complexes, [(p-NO2-C6H4–(O)C=N–N=C(Ph)–(Ph)C=N–N=C(O)–(p-OCH3-C6H4))Sn(n-Bu)2] (S01), [(p-OCH3-C6H4–(O)C=N–N=C(Ph)–(Ph)C=N–N=C(O)–(p-OCH3-C6H4))Sn(n-Bu)2(CH3OH)](S02), and [(p-OH-C6H4–(O)C=N–N=C(Ph)–(Ph)C=N–N=C(O)–(p-OH-C6H4))Sn(n-Bu)2]·4CH3OH (S03), were synthesized via the reaction of biphenyl ethylene dione benzoyl hydrazine with dibutyltin oxide (Scheme 1). All complexes were characterized using infrared (IR) spectra, 1H, 13C, and 119Sn nuclear magnetic resonance (NMR) spectra, and high-resolution mass spectrometry, and crystal structures were determined using X-ray diffraction. In addition, we further investigated the anticancer activity and mechanism of the complexes in vitro. Complex S03 had extremely strong anticancer activity in vitro and killed cancer cells through multiple mechanisms. Thus, complex S03 is a potential antitumor agent for delaying or overcoming chemotherapy resistance. This study provides new insights for the further development of novel organotin metal complexes as antitumor agents.