Identification of Helicobacter pylori-carcinogenic TNF-alpha-inducing protein inhibitors via daidzein derivatives through computational approaches.

Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.

Engineering the surface patchiness and topography of polystyrene colloids: From spheres to ellipsoids.

HYPOTHESIS: Colloidal surface morphology determines suspension properties and applications. While existing methods are effective at generating specific features on spherical particles, an approach extending this to non-spherical particles is currently missing. Synthesizing un-crosslinked polymer microspheres with controlled chemical patchiness would allow subsequent thermomechanical stretching to translate surface topographical features to ellipsoidal particles. EXPERIMENTS: A systematic study using seeded emulsion polymerization to create polystyrene (PS) microspheres with controlled surface patches of poly(tert-butyl acrylate) (PtBA) was performed with different polymerization parameters such as concentration of tBA monomer, co-swelling agent, and initiator. Thermomechanical stretching converted seed spheres to microellipsoids. Acid catalyzed hydrolysis (ACH) was performed to remove the patch domains. Roughness was characterized before and after ACH using atomic force microscopy. FINDINGS: PS spheres with controlled chemical patchiness were synthesized. A balance between two factors, domain coalescence from reduced viscosity and domain growth via monomer absorption, dictates the final PtBA) patch features. ACH mediated removal of patch domains produced either golf ball-like porous particles or multicavity particles, depending on the size of the precursor patches. Patchy microspheres were successfully stretched into microellipsoids while retaining their surface characteristics. Particle roughness is governed by the patch geometry and increases after ACH. Overall, this study provides a facile yet controllable platform for creating colloids with highly adjustable surface patterns.