Binding mechanism of anacardic acid, carnosol and garcinol with PCAF: A comprehensive study using molecular docking and molecular dynamics simulations and binding free energy analysis.

The p300/CBP associated factor bromodomain (PCAF Brd) is emerged as one of the promising target proteins for different types of cancers. PCAF is one among the histone acetyltransferase enzymes which involved in the regulation of transcriptase process by modifying the chromatin structure. Anacardic acid, carnosol, garcinol are the experimentally reported inhibitors of PCAF Brd; however, their detailed binding mechanism these inhibitors are not yet known. The intermolecular interaction, binding energy, and the stability of these inhibitors with the active site of PCAF Brd are playing the key role in the binding of these inhibitors with PCAF. The in silico study incorporates the molecular docking and dynamics simulations; these molecular level simulations allow to understand the binding mechanism. In the present study, the induced fit molecular docking and molecular dynamics of anacardic acid, carnosol and garcinol molecules against the PCAF Brd have been performed. The docking score values of these molecules are -5.112 (anacardic acid), -5.141 (carnosol), -5.199 (garcinol) and -3.641 (L45) kcal/mol, respectively. Further, the molecular dynamics simulation was carried out for these docked complexes to understand their conformational their stability and binding energy from the roots means square deviation (RMSD) and root means square of fluctuation (RMSF), and molecular mechanics with the generalized born and surface area solvation (MM/GBSA) binding free energy calculations. The intermolecular interactions and binding free energy values confirm that garcinol forms key interactions and has high binding affinity towards PCAF Brd on compare with the other two inhibitors. Therefore, garcinol may be considered as a potential inhibitor of PCAF Brd.

Gelatin/polyvinyl alcohol loaded magnesium hydroxide nanocomposite attenuates neurotoxicity and oxidative stress in Alzheimer's disease induced rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, mitochondrial and cholinergic dysfunction are key indicators of Alzheimer's disease (AD). In this study, gelatin and polyvinyl alcohol (PVA) were tethered with magnesium hydroxide (Mg(OH)2) to synthesize nanocomposite (Ge/PVA/Mg(OH)2) through alkali co-precipitation. The characterization studies using FT-IR, XRD, DLS, and SEM-EDX confirmed the successful formation of Ge/PVA/Mg(OH)2 nanocomposite. Further, in vitro study it clearly demonstrated the impact of Ge/PVA/Mg(OH)2 nanocomposite on biocompatibility, cellular uptake, reduced Aß protein expression and protection of neuronal cell death. The confocal study further confirmed the down-regulation of Aß expression. The subsequent in vivo analysis witnessed the protective effect of Ge/PVA/Mg(OH)2 nanocomposites on the cognitive and synaptic impairments of AD in intraceribroventricular streptozotocin (ICV-STZ) treated rats. Oxidative stress, antioxidant enzymes, cholinergic and mitochondrial complex activity were conducted and revealed that the Acetylcholineesterase (AChE) and Malondialdehyde (MDA) activities were significantly decreased by contrast the antioxidant enzyme activities were found to be increased in the cortex and hippocampus regions of the brain. Thus, the present investigation recommends Ge/PVA/Mg(OH)2 nanocomposite to target AD and clinical translation.

Salt formation, hydrogen-bonding patterns and supramolecular architectures of acridine with salicylic and hippuric acid molecules.

The intermolecular interactions and salt formation of acridine with 4-aminosalicylic acid, 5-chlorosalicylic acid and hippuric acid were investigated. The salts obtained were acridin-1-ium 4-aminosalicylate (4-amino-2-hydroxybenzoate), C13H10N+·C7H6NO3- (I), acridin-1-ium 5-chlorosalicylate (5-chloro-2-hydroxybenzoate), C13H10N+·C7H4ClO3- (II), and acridin-1-ium hippurate (2-benzamidoacetate) monohydrate, C13H10N+·C9H8NO3-·H2O (III). Acridine is involved in strong intermolecular interactions with the hydroxy group of the three acids, enabling it to form supramolecular assemblies. Hirshfeld surfaces, fingerprint plots and enrichment ratios were generated and investigated, and the intermolecular interactions were analyzed, revealing their quantitative contributions in the crystal packing of salts I, II and III. A quantum theory of atoms in molecules (QTAIM) analysis shows the charge-density distribution of the intermolecular interactions. The isosurfaces of the noncovalent interactions were studied, which allows visualization of where the hydrogen-bonding and dispersion interactions contribute within the crystal.