Gastric carcinoma with over one million new cases and 769,000 deaths in 2020, ranks fifth in morbidity and fourth in mortality worldwide, and has the highest incidence in East Asia [1]. For patients with advanced gastric cancer, the 5-year survival rate is less than 5 %, chemotherapy is the main treatment option for advanced gastric cancer patients. There are few targeted therapies for gastric cancer, fluorouracil, oxaliplatin and other cytotoxic drugs are still the first-line drugs for gastric cancer chemotherapy [2], [3]. However, due to drug resistance and toxic side effect, chemotherapy usually fails in clinical practice. Therefore, the development of new high-efficiency and low-toxic chemotherapy drugs has very important clinical significance. Designing new drugs based on natural products is an important part of new anti-tumor drug research [4], [5].

Curcumin is the main active ingredient in traditional Chinese medicine turmeric, and it has a variety of biological activities, such as anti-inflammatory, anti-tumor and so on [6], [7]. Curcumin is a polyphenol compound containing two substituted benzene rings, and there is a 7-carbon conjugated bridge between the two benzene rings, and there is an unstable β-diketone structure in the bridge. Due to the unstable structure of β-diketone, curcumin has less absorption, rapid metabolism and low bioavailability, which greatly limits its application [8]. So far, there have been many clinical trials of curcumin, none of which have been successful, and the pharmacokinetic defect is the main reason. Deleting a carbonyl group in its β-diketone and transforming it into a monocarbonyl curcumin analogs (MCAs) can not only improve the stability, but also retain its antitumor activity [9], [10]. However, this transformation shortened the length of the carbon chains linked by the benzene rings. The safety and activity of MCAs are related to the type of bridging ketone in the middle of its molecular skeleton, and the bridging ketone as cyclopentanone has the lowest toxicity [11], [12], [13]. Cinnamon, the dried bark of Cinnamomum cassia Pres, has been widely concerned for its strong anti-tumor activity [14], [15]. Cinnamaldehyde is the main active component of cinnamon, which contains many chemical components [14], [15]. It has been reported that cinnamaldehyde can inhibit tumor cell proliferation, induce tumor cell apoptosis, interfere with tumor cell cycle and suppresses tumor cell epithelial-mesenchymal transformation through various ways, exhibiting good anti-tumor activity in a variety of malignant tumors [16], [17]. Its molecular regulatory mechanism involves several cell signaling pathways, such as phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT) signaling pathway and autophagy related signaling pathway [18], [19], [20]. Therefore, MCAs and cinnamaldehyde can be used as potential structures for the design of anti-tumor compounds.

In this study, according to the principle of pharmaceutical chemistry, we combined the molecular skeleton of the MCAs with cyclopentanone as the bridging ketone into the cinnamaldehyde structure with good biological activity, and designed a class of molecules with benzene rings at both ends (Fig. 1). A new class of MCAs with 7-carbon-links was designed, and the anti-gastric cancer activity and structure–activity relationship of the compound were studied.