Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents

Abstract

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a–c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a–c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

Novel 1,2,3-Triazole-sulphadiazine-ZnO Hybrids as Potent Antimicrobial Agents against Carbapenem Resistant Bacteria

“…All click adducts 3a – c showed similar proton and carbon spectral data to those previously reported in our study [ 25 ]. The absence of the characteristic alkyne protons and carbons in their spectra and the appearance of diagnostic 1,2,3-triazolyl proton signals in the aromatic region confirmed their formation.…”

“…The targeted 1,2,3-triazoles with sulfa-drug tethers were re-synthesized using our recently reported click procedure [ 25 ], as shown in Scheme 1 . Click synthesis first required diazotization of sulfadiazine, sulfapyridine, and/or sulfaguanidine, followed by treatment with sodium azide to provide the corresponding sulfadiazine azides 1a – c .…”

“…The click products 3a – c were prepared and resynthesized in accordance with our previous work [ 25 ]. Detailed synthesis steps and compounds characterizations were added as Supplementary Materials (Figures S1 and S2)…”

“…The targeted 1,2,3-triazoles with sulfa-drug tethers were re-synthesized using our recently reported click procedure [25], as shown in Scheme 1. Click synthesis first required diazotization of sulfadiazine, sulfapyridine, and/or sulfaguanidine, followed by treatment with sodium azide to provide the corresponding sulfadiazine azides 1a-c. Next, under optimized Cu(I)-assisted alkyne-azide cycloaddition conditions (CuSO 4 , Na-ascorbate; DMSO/H 2 O (1:1); 6-10 h room temperature), the freshly prepared sulfonamide azides were subsequently ligated to propargyl alcohol, yielding the desired 1,2,3-triazole-sulfonamide molecular conjugates 3a-c in 86-90 percent yields.…”

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

“…The most e cient certi ed drugs are pyrimethamine-derived sulfadiazine, sulfamerazine, sulfamethazine, and sulfapyridine (Figure 1) as the pyrimethamine is constantly present in the greater part of drug treatments. These intriguing scaffolds motivated us to design and generate new focused 1,2,3-triazolesulfonamide molecular conjugates that simulate the perfectly matched inhibition properties of T. gondii of the certi ed drugs as continuation to our previous work [52]. In the present work, we focused our design on mimicking the certi ed medications, notably the most potent amino groups, which are known to be critical attributes in the interaction with the receptor protein via hydrogen bonding, resulting in enhanced biological activity [53].…”