Abstract
Ursolic acid (UA), a plant-derived compound, has many properties beneficial to health. In the present study, we synthesised three series of novel UA derivatives and evaluated their anti-Toxoplasma gondii activity both in vitro and in vivo. Most derivatives exhibited an improved anti-T. gondii activity in vitro when compared with UA (parent compound), whereas compound 3d exhibited the most potent anti-T. gondii activity in vivo. Spiramycin served as the positive control. Additionally, determination of biochemical parameters, including the liver and spleen indexes, indicated compound 3d to effectively reduce hepatotoxicity and significantly enhance anti-oxidative effects, as compared with UA. Furthermore, our molecular docking study indicated compound 3d to possess a strong binding affinity for T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Based on these findings, we conclude that compound 3d, a derivative of UA, could act as a potential inhibitor of TgCDPK1.
Highlights
Toxoplasma gondii is an opportunistic pathogen that causes infection in human beings and various animals, thereby severely impairing their health
Considering the increasing percentage of natural product-based drugs in the market in the past years, researchers have focussed their attention to plant-based compounds with anti-T. gondii activity
Ursolic acid (UA)-1 was obtained by Jones oxidation of UA at 0 C
Summary
Toxoplasma gondii is an opportunistic pathogen that causes infection in human beings and various animals, thereby severely impairing their health. Traditional anti-T. gondii drugs have various disadvantages, such as the inability to completely kill the protozoa and oocysts, high toxicity, frequent recurrence, and failure in immuno-compromised individuals[2,3]. Considering the increasing percentage of natural product-based drugs in the market in the past years, researchers have focussed their attention to plant-based compounds with anti-T. gondii activity. Several studies have shown natural products and their derivatives to exert strong anti-T. gondii effects, making these an attractive source of anti-T. gondii drugs[4,5]. In this regard, structural modifications of natural products to generate effective and less-toxic derivatives are considered to be very promising for the development of anti-T. gondii drugs
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