In vitro activity and moderate in vivo efficacy of a novel β-carboline derivative against acute Toxoplasma gondii tachyzoites.

Toxoplasma gondii is a globally important zoonotic pathogen that causes widespread infections in both human and animal populations. Current pharmacological treatments for toxoplasmosis are plagued by considerable limitations, highlighting the urgent demand for novel therapeutic agents with hight efficacy and low toxicity. β-carboline (βC) alkaloids, due to their inherent biological activities, represent promising candidates with substantial therapeutic potential. In this study, we designed and synthesized a novel β-carboline derivative, H-168-B, and systematically evaluated its anti-T. gondii activity through both in vitro and in vivo experiments. In vitro assays revealed that H-168-B exhibited relatively low cytotoxicity in Vero cells (cell viability >90%) and effectively inhibited the proliferation of T. gondii tachyzoites (IC₅₀ = 34.52 μM). Additionally, plaque assays conducted in HFF cells showed a dose-dependent decrease in plaque formation, with near-complete inhibition observed at 100 μM. This concentration also significantly impaired parasite invasion and intracellular replication. In an infected ICR mouse model, H-168-B treatment stabilized body weight, extended mouse survival time by 30%, and exerted moderate organ-protective effects compared with sulfadiazine. Collectively, these results identify H-168-B as a promising novel anti-parasitic compound warranting further investigation.