Synthesis and Anti-Toxoplasma Activity In vitro of Arctigenin Derivatives

Background: At present, the therapeutic drugs for Toxoplasmosis have serious side effects and limitations in application, so it is urgent to develop low-toxicity and high-efficiency drugs. Objective: A series of new derivatives based on arctigenin were designed and synthesized, aiming to obtain target derivatives with superior anti-Toxoplasma activity. Methods: A series of quinoline groups were introduced into the phenolic hydroxyl group of arctigenin compound, and 29 novel arctigenin derivatives were designed and synthesized. The chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. The cytotoxicity of all compounds to host cells (HeLa) and the half inhibitory concentration of HeLa cells infected with Toxoplasma gondii were determined by the MTT assay, and the selectivity index (SI) was calculated. Results: The selectivity index of compounds B8 and B12 was 1.45, indicating the anti-Toxoplasma activity of compound B8 and B12 to be higher than that of the lead compound arctigenin (SI= 0.99) and the positive control drug spiramycin (SI= 0.92). Conclusion: Compounds B8 and B12 demonstrated the most potent anti-Toxoplasma activity, with an SI value of 1.45. This offers valuable guidance for the subsequent screening of more effective anti-Toxoplasma drugs.