nitd-609 and Toxoplasmosis

Toxoplasma gondii severely threaten the health of immunocompromised patients and pregnant women as this parasite can cause several disease, including brain and eye disease. Current treatment for toxoplasmosis commonly have high cytotoxic side effects on host and require long durations ranging from one week to more than one year. The regiments lack efficacy to eradicate T. gondii tissue cysts to cure chromic infection results in the needs for long treatment and relapsing disease. In addition, there has not been approved drugs for treating the pregnant women infected by T. gondii. Moreover, Toxoplasma vaccine researches face a wide variety of challenges. Developing high efficient and low toxic agents against T. gondii is urgent and important. Over the last decade, tremendous progress have been made in identifying and developing novel compounds for the treatment of toxoplasmosis. This review summarized and discussed recent advances between 2009 and 2019 in exploring effective agents against T. gondii from five aspects of drug discovery.

Topics: Animals; Antiprotozoal Agents; Drug Discovery; Female; Humans; Pregnancy; Toxoplasma; Toxoplasmosis

Here, we show that spiroindolone, an effective treatment for plasmodia, is also active against Toxoplasma gondii tachyzoites. In vitro, spiroindolone NITD609 is cidal for tachyzoites (50% inhibitory concentration [IC50], 1μM) and not toxic to human cells at ≥10μM. Two daily oral doses of 100 mg/kg of body weight reduced the parasite burden in mice by 90% (P=0.002), measured 3 days after the last dose. This inhibition of T. gondii tachyzoites in vitro and in vivo indicates that spiroindolone is a promising lead candidate for further medicine development.

Topics: Adenosine Triphosphatases; Animals; Coccidiostats; Humans; In Vitro Techniques; Indoles; Mice; Microbial Sensitivity Tests; Spiro Compounds; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Animal