Toxoplasmosis, which affects more than a billion people worldwide, is a common parasitic infection
caused by the obligate intracellular parasite, Toxoplasma gondii. Current treatment strategies have several
limitations, including unwanted side effects and poor efficacy. Therefore, newer therapies are needed for
toxoplasmosis. Drug repurposing and screening of a vast array of natural and/or synthetic compounds is a
viable option for antiparasitic drug discovery. In this study, we screened 62 compounds comprising natural
products (NPs†) and FDA-approved (FDA) drugs, to identify the hit compounds that suppress the growth
of T. gondii. To determine the parasite inhibitory potential of the compounds, host mammalian cells were
infected with a transgenic T. gondii strain, and the viability of the parasite was evaluated by luminescence.
Of the 62 compounds, tubericidin, sulfuretin, peruvoside, resveratrol, narasin and diacetoxyscirpenol of
the natural product isolates, as well as bortezonib, 10-Hydroxycamtothecin, mebendazole, niflumic acid,
clindamycin HCl, mecamylamine, chloroquine, mitomycin C, fenbendazole, daunorubicin, atropine, and
cerivastatin of FDA molecules were identified as “hits” with ≥ 40 percent anti-parasite action. Additionally,
mitomycin C, radicicol, naringenin, gitoxigenin, menadione, botulin, genistin, homobutein, and gelsemin
HCl of the natural product isolates, as well as lomofungin, cyclocytidine, prazosin HCl, cerivastatin,
camptothecin, flufenamic acid, atropine, daunorubicin, and fenbendazole of the FDA compounds exhibited
cytotoxic activity, reducing the host viability by ≥ 30 percent. Our findings not only support the prospects
of drug repurposing, but also indicate that screening a vast array of molecules may provide viable sources
of alternative therapies for parasitic infection
