Diabetes mellitus (DM) is a real challenge to the recent era and is one of the major diseases for initiating life-threatening disorders. In current research, a compound was designed by combining vanillin, thiazolidinedione and morpholine. The goal of our designed work is to demonstrate the ability of our design compound (9) to modulate more than one target responsible for hyperglycemia at the same time. The synthesized compound was able to show good to moderate inhibition potential against α-glucosidase, α-amylase and protein tyrosine phosphatase 1B. However, it exhibited excellent in-vitro inhibition of Dipeptidyl peptidase-4 (DPP-4) with IC₅₀ value of 0.09 µM. Antioxidant activity by using DPPH assay also showed its good antioxidant potential. In in-vivo experiments, the compound 9 was proved to be safe in experimental mice. The activity profile of the compound was observed for 21 days which showed that the compound was also effective in experimental mice. Binding orientations and Interactions with key amino acid residues of the selected targets were also studied by using docking studies. Overall, we were successful in synthesizing multitarget preclinical therapeutic by combining three pharmacophoric moieties into a single chemical entity that can modulate more than one target at the same time.

Alshehri DB, et al. Pediatr Gastroenterol Hepatol Nutr. 2022 May;25(3):163-179. https://doi.org/10.5223/pghn.2022.25.3.163

Ghrelin is a peptide hormone with direct or indirect effects on obesity and asthma. More data are required to understand the effect of ghrelin on the control and pathogenesis of these diseases. The aim of this study was to evaluate ghrelin levels in selected groups of children to identify the association between serum ghrelin, obesity, and the severity of asthma. The study included 401 school children selected from the Najran area and grouped into non-obese asthmatics, obese asthmatics, obese non-asthmatics and controls (non-obese non-asthmatics). Blood levels of ghrelin, interleukin (IL)-4, IL-5 and IL-21 were determined by ELISA. The mean ghrelin values were insignificantly increased in obese children compared with non-obese children. The highest blood ghrelin values were in the non-obese asthmatic group. Serum ghrelin, IL-4 and IL-21 levels were significantly increased in asthmatic children compared with non-asthmatic children (p < 0.05), and there were significant positive correlations between ghrelin and IL-4, IL-5, and IL-21 in asthmatic children. Furthermore, ghrelin, IL-4, and IL-21 levels were significantly higher in uncontrolled asthmatics compared with controlled-asthmatic children (p < 0.05). Asthma was the only significant risk factor for high ghrelin values. This study provides evidence supporting the anti-inflammatory role of ghrelin in the pathogenesis of asthma. Asthma might be considered as an important determinant of high ghrelin values in children.

Background: The primary carrier of bile acids in humans is the bile salt export pump (BSEP). which are crucial for the digestion and absorption of fat. Type 2 progressive familial intrahepatic cholestasis (PFIC-2), which is brought on when BSEP is suppressed and causes a decrease in bile flow and a buildup of cytotoxic bile salts in the liver, is one of the main causes of cholestasis in Saudi Arabia. Elucidate the inhibitory potential with minimal or no adverse effects.Methods: The structure (6LR0) was downloaded from the PDB. Protein active sites were anticipated because these are pockets where ligands can bind and perform reactions to treat an infection. The PubChem zinc and mpd3 databases were used to get the ligands' structures. Molecular operating environment (MOE) was utilized to perform molecular docking of 1600 phytochemicals against BSEP. LigX was used to observe the docking hits for interaction analysis. Results: identification of 4 potential candidates for binding to the BSEP active site. then, Protox II-was used to forecast toxicity for the selected hits. Molecular dynamics simulations were also used to assess the binding complex's stability in water for 100 nanoseconds. The strong binding affinity of high-ranked drugs was predicted by our molecular docking and simulation.Conclusions: This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the BSEP. The aim of this research is to identify novel -BSEP drug targets, and in future in vitro and in vivo research could prove its clinical efficiency.