Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles

Abstract

Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii). Promising novel compounds for the treatment of T. gondii are introduced in the current investigation. In order to test their in vitro potency against T. gondii tachyzoites, six 1,2,3-triazoles-based sulfonamide scaffolds with terminal NH2 or OH group were prepared and investigated as sulfadiazine equivalents. When compared to sulfadiazine, which served as a positive control, hybrid molecules showed much more anti-Toxoplasma activity. The results showed that the IC50 of the examined compounds 3(a–f) were recoded as 0.07492 μM, 0.07455 μM, 0.0392 μM, 0.03124 μM, 0.0533 μM, and 0.01835 μM, respectively, while the sulfadiazine exhibited 0.1852 μM. The studied 1,2,3-triazole-sulfadrug molecular conjugates 3(a–f) revealed selectivity index of 10.4, 8.9, 25.4, 21, 8.3, and 29; respectively. The current study focused on the newly synthesized amino derivatives 3(d–f), as they contain the more potent amino groups which are recognized to be essential elements and promote better biological activity. Extracellular tachyzoites underwent striking morphological alterations after 2 h of treatment as seen by scanning electron microscopy (SEM). Additionally, the intracellular tachyzoite exposed to the newly synthesized amino derivatives 3(d–f) for a 24-h period of treatment revealed damaged and altered morphology by transmission electron microscopic (TEM) indicating cytopathic effects. Moreover, compound 3f underwent the most pronounced changes, indicating that it had the strongest activity against T. gondii.

The role of Nrf2 signaling in parasitic diseases and its therapeutic potential

“…Sulfadiazine and pyrimethamine are the most effective available therapeutic agents used to treat toxoplasmosis. While these drugs can cause serious side effects, researchers are looking for new alternatives that are both effective and less toxic [ 81 , 99 ]. Inonotus obliquus polysaccharide (IOP) is one of these newly considered alternatives with both antioxidative and anti-inflammatory activities [ 92 , [100] , [101] , [102] , [103] , [104] , [105] ].…”

Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer

“…24 It was noticeable that the hybridization of the tunable 1,2,3-triazole scaffolds with various pharmacophores has proven more beneficial and essential in discovering significant bioactive and efficient candidates. [25][26][27] Our main efforts have been mainly devoted to the research and development of novel approaches for synthesizing new heterocyclic hybrid compounds, beginning with particular biologically functionalized constituents, [28][29][30][31][32][33][34][35] and exploring the biological significance of benzene sulfonamides, which constitute an important class of organic compounds with high potency and selectivity against parasitic, bacterial, fungal, and cancer cells, [36][37][38][39] along with the broad pharmacological spectrum of the 1,2,3-triazole nucleus, [40][41][42][43] resulting in their selection as preferred frameworks for library design and the generation of tailored therapeutic agents. [44][45][46][47] Furthermore, their possession of numerous functions in the structures has resulted in a resurgence of interest in improving their synergetic effects.…”