Design, Synthesis, and In-Silco ADME Prediction of Some Novel Bis(1,3,4-thiadiazoles) Encapsulated Lipid-chitosan Nano Capsule Decorative with Magnetic Nanoparticles and Their Potential Anti-helicobacter Pylori Activity

Helicobacter pylori (H. pylori) is an extremely prevalent human pathogen globally that leads to severe illnesses. Sadly, the worldwide issue of H. pylori's resistance to antimicrobial medications persists. In this context, creating an anti-H. pylori vaccine that can deliver a satisfactory eradication rate with fewer side effects would be highly beneficial. In this regard, a new series of bis(1,3,4-thiadiazoles) was synthesized and assessed for antimicrobial activity against H. pylori. Combining two bioactive 1,3,4-thiadiazole portions within a single molecule to create a new bis-heterocycle represents an efficient strategy to produce powerful compounds and address issues of resistance and effectiveness. Every synthesized compound showed outstanding inhibition results. Compounds 5c and 8 exhibited the lowest MIC values, recorded at 7.5 and 15.6 μg/mL, respectively. Theoretical predictions were employed to evaluate ADME, leading to outcomes of low solubility, stability, and bioavailability. The effective agents aimed at H. pylori were encapsulated in an appropriate newly developed nanocarrier to tackle challenges related to low bioavailability and stability. Further tests were carried out to evaluate the efficacy of antimicrobials against H. pylori, resulting in promising results. Additionally, the MIC values decreased by 4 and 2 times relative to their original synthetic versions. The activity of the enzyme urease was assessed before nanoencapsulation, showing an IC value of 8.99 μg/mL, which was reduced to 7.8 μg/mL after nanoencapsulation.