Promising anti-Toxoplasma activity of 1,2,3-triazole tethering sulfonamide moiety; synthesis; characterization and in vitro study

Abstract

Background Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T.gondii). The current study introduces new lead compounds for the treatment of T.gondii. Methods Three novel 1,2,3-triazoles-based sulfonamide scaffold were designed, synthesized and fully characterized in order to investigate the In vitro toxoplasmacidal potency using Vero cells as host for T. gondii. Selectivity index parameter was used to express compounds efficacy in the inhibition of T. gondii proliferation, whereas the scanning electron microscopy technique was used to assess the ultrastructural changes. A significant anti-toxoplasma activity was observed with hybrid molecules compared to the sulfadiazine as a positive control. Results The results showed that the IC50 (inhibitory concentration) of the investigated compounds 3(a,b,c) were recoded as 10.335 µg/ml, 20.106 µg/ml and 5.574 µg/ml, respectively; while the used sulfadiazine exhibited 49.794 µg/ml as IC50. The investigated 1,2,3-triazole-sulfadrug molecular conjugates 3(a,b,c) revealed selectivity index at 21.028, 8.356, 28.595, respectively. All compounds were highly selective than the gold standard drug which showed selectivity index of 7. Scanning electron microscopy (SEM) revealed that most tachyzoites had remarkable morphological changes after 2 hours of exposure. Conclusions These results indicate that these new candidates 3(a,b,c) have the potential to be a viable source of antiparasitic therapeutic agents, and compound 3c exhibits the highest activity against T. gondii.