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Updated: Jul 2, 2026
A Genetic Screen to Isolate Toxoplasma gondii Host-cell Egress Mutants
Published on: February 8, 2012
Identification of potential dual -targets anti- toxoplasma gondii compounds through structure-based virtual screening
Nurul Hanim Salin1, Rahmah Noordin2, Belal O Al-Najjar3
1Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Gelugor, Pulau Pinang, Malaysia.
Abstract:
Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease which can lead to morbidity and mortality of the fetus and immunocompromised individuals. Due to the limited effectiveness or side effects of existing drugs, the search for better drug candidates is still ongoing. In this study, we performed structure-based screening of potential dual-targets inhibitors of active sites of T. gondii drug targets such as uracil phosphoribosyltransferase (UPRTase) and adenosine kinase (AK). First screening of virtual compounds from the National Cancer Institute (NCI) was performed via molecular docking. Subsequently, the hit compounds were tested in-vitro for anti- T. gondii effect using cell viability assay with Vero cells as host to determine cytotoxicity effects and drug selectivities. Clindamycin, as positive control, showed a selectivity index (SI) of 10.9, thus compounds with SI > 10.9 specifically target T. gondii proliferation with no significant effect on the host cells. Good anti- T. gondii effects were observed with NSC77468 (7-ethoxy-4-methyl-6,7-dihydro-5H-thiopyrano[2,3-d]pyrimidin-2-amine) which showed SI values of 25. This study showed that in-silico selection can serve as an effective way to discover potentially potent and selective compounds against T. gondii.
Insights
Researchers discovered a new compound, NSC77468, that effectively targets Toxoplasma gondii proliferation. This in-silico drug discovery method shows promise for developing selective treatments against toxoplasmosis, particularly for vulnerable populations.
Area of Science:
- Parasitology
- Drug Discovery
- Computational Chemistry
Background:
- Toxoplasma gondii causes toxoplasmosis, a significant threat to fetal and immunocompromised individuals.
- Existing treatments for toxoplasmosis have limitations in efficacy and safety, necessitating new drug development.
Purpose of the Study:
- To identify novel, selective dual-target inhibitors for T. gondii.
- To evaluate potential drug candidates using structure-based screening and in-vitro assays.
Main Methods:
- Structure-based virtual screening of National Cancer Institute (NCI) compounds using molecular docking.
- In-vitro anti- T. gondii activity assessment using cell viability assays.
- Cytotoxicity evaluation and selectivity index (SI) determination against Vero cells.
Main Results:
- NSC77468 demonstrated potent anti- T. gondii activity with a selectivity index (SI) of 25, significantly higher than the positive control Clindamycin (SI=10.9).
- The compound selectively targets T. gondii proliferation with minimal impact on host cells.
- In-silico screening successfully identified a potent and selective anti- T. gondii candidate.
Conclusions:
- In-silico drug discovery is an effective strategy for identifying selective T. gondii inhibitors.
- NSC77468 represents a promising lead compound for developing new toxoplasmosis therapies.
- Further research into dual-target inhibitors could yield improved treatments for toxoplasmosis.
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