Synthesis and Biological Activity of Chalcone Derivatives Containing Thiazoxime Ethers

In this paper, a series of chalcone derivatives containing thiazole oxime ether structures were designed and synthesized from the natural product chalcone. The structures of these compounds were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The results of antiviral activity tests showed that some of the target compounds exhibited better inhibition. Among them, S3, S4, and S16 exhibited better therapeutic activities with EC₅₀ values of 18.6, 66.9, and 61.8 μg/mL, respectively, which were superior to that of the control drug ningnanmycin (158.3 μg/mL). The target compound S3 showed good protective activity with an EC₅₀ of 88.6 μg/mL, which was better than that of ningnanmycin (175.6 μg/mL). The results of microscale thermophoresis (MST) demonstrated that S3 and S13 exhibited strong binding affinity to tobacco mosaic virus capsid protein (TMV-CP), with Kd values of 0.0013 μM and 0.5397 μM, respectively. These values were significantly lower than that of ningnanmycin (Kd = 0.6509 μM). The molecular docking results showed that the hydrogen bonds between S3 and the key amino acid residues of TMV-CP had shorter bond lengths and were more tightly bound than those of ningnanmycin.