Synthesis and in vitro anti-Toxoplasma gondii activity of a new series of aryloxyacetophenone thiosemicarbazones.

Abstract

A new series of aryloxyacetophenone thiosemicarbazones 4a-q have been synthesized as anti-Toxoplasma gondii agents. All compounds showed significant inhibitory activity against T. gondii-infected cells (IC50 values 1.09-25.19μg/mL). The 4-fluorophenoxy derivative (4l) was the most potent compound with the highest selectivity toward host cells (SI = 19), being better than standard drug pyrimethamine. SAR study indicated that the concurrence of proper substituents on both aryl ring of phenoxyacetophenone is important for potency and safety profile. Further in vitro experiments with the representative compounds 4l and 4p revealed that these compounds at the concentration of 5μg/mL can significantly reduce the viability of T. gondii tachyzoites, as well as their infectivity rate and intracellular proliferation, comparable to those of pyrimethamine.