Superior rat wound-healing activity of green synthesized silver nanoparticles from acetonitrile extract of Juglans regia L: Pellicle and leaves.

The process of wound healing is complicated. Antimicrobial silver has been one of the substances used for wounds since ancient times. Moreover, traditional medicine has long used Juglans regia L. to promote wound healing. Since eco-friendly nanotechnology has various uses in biomedical research, the aim of this study was to assess the wound-healing capacity of bio-reduced silver nanoparticles (AgNPs). UV, DLS, TEM, and FTIR were used to characterize the prepared AgNPs. Pellicle's bioreduced AgNP (AgNP/P) has a better polydispersity index (PI) of 0.336 compared to its chemically synthesized peers, which have a PI of 0.67. Using incision and excision wound healing models, AgNPs and extracts were compared to Solcoseryl®. Skin-breaking strength, wound contraction, epithelialization time, histology, and cytokines were all assessed. Juglans regia L. pellicle extract (P) has shown significant effectiveness in both models, as well as their bio-reduced partner AgNP/P. The skin's tensile strength following AgNP/P therapy (871 g, p value < 0.05) is comparable to that after Solcoseryl® (928 g), both of which are significantly better than AgNP (592 g) in the incision wound model. Epithelialization time (16.0 and 16.5 days) did not substantially differ from Solcoseryl® (15.3 days) (P value < 0.05). There was an elevated collagen content. Low levels of IL1ß (189.0 pg/g) and high levels of TNF-α (1007.1 pg/g) in the case of AgNP/P suggest various cellular kinds of maturation and various wound healing structures that are evident in histopathology investigations. The bioreduced AgNP/P could find use as a pharmaceutical agent for wound healing dressings.

Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin delivery.

Mesoporous silica nanoparticles (MSNs) gained significant attention, particularly in the pharmaceutical field. Folic acid (FA) shows marked promise as a targeting agent for its specific interaction with the folate receptor. This receptor is over-expressed on the cell surface of several cancerous cells like breast cancer. Polyethylene glycol (PE), as well as polypropylene glycol (PEG), is used to decorate nanoparticles to improve their biodistribution. Moreover, carboxymethyl beta-cyclodextrin (CM-ß-CD), is used as a complexation molecule. In this study, we described the chemical synthesis, in vitro drug release and antiproliferative activity of doxorubicin-loaded/decorated MSNs further coupled with FA in two conditions: chemically bound or as a complex with CM-ß-CD. Fourier Transform Infrared Spectroscopy with Transmission Electron Microscopy confirmed the successful surface change. Dynamic Light Scattering confirmed the change in surface characters like zeta potential, polydispersity index (PI), and size. PI improved from 0.58 to 0.23 while the size enlarged from 200 to 348 and 532 nm. Functionalized nanoparticles demonstrated more significant drug entrapment with (97%) while undecorated MSNs only showed (63%). Accordingly, we effectively synthesized FA-PEG2000-MSNs with IC50: 0.015 mg/mL targeting HeLa cells. This approach may allow potential applications as a drug delivery system in cancer chemotherapy.HighlightsMesoporous silica nanoparticles (MSNs) with a carboxylic acid or amine surface group can be successfully decorated with long-chain hydrophilic polymer via an amide bond.Carboxymethyl-ß-cyclodextrin coupled with long-chain polymer as host to form a complex with targeting molecule folic acid.Folic acid can be anchored directly to a polymer coat.TEM; DLS and FTIR confirmed the surface modification.The drug encapsulation efficiency; cytotoxicity and selectivity of functionalized nanoparticles with PEG and conjugated with FA were the best.Chemical modification has improved cytotoxicity of doxorubicin and selectivity against Hela cells.

Discovery of new Gyrase ß inhibitors via structure based modeling.

Gyrase B is an essential enzyme in the prokaryotes which became an attractive target for antibacterial agents. In our study, we implemented a wide range of docking configurations to dock 120 inhibitors into the in the ATP- binding pocket of Gyrase B enzyme (PDB code: 4GEE). LigandFit docking engines and six scoring functions were utilized in the study. Furthermore, the ligands were docked in their ionized and unionized forms into the hydrous and anhydrous binding pocket. We used docking-based Comparative Intermolecular Contacts Analysis (db-CICA) which is a novel methodology to validate and identify the optimal docking configurations. Three docking configurations were found to achieve self-consistent db-CICA models. The resulting db-CICA models were used to construct corresponding pharmacophoric models that were used to screen the National Cancer Institute (NCI) list of compounds. In-vitro study represents antibacterial activities for twelve hit molecules with the most active having IC50 of 20.9 µM.

Discovery of nanomolar phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors using ligand-based modeling and virtual screening followed by in vitro analysis.

Phosphoinositide 3-kinase gamma (PI3Kγ) is member of a family of enzymes involved in cancer pathogenesis. Accordingly, considerable efforts have been carried out to develop new PI3Kγ inhibitors. Towards this end we explored the pharmacophoric space of PI3Kγ using three diverse sets of inhibitors. Subsequently, we employed genetic algorithm-based QSAR analysis to select optimal combination of pharmacophoric models and physicochemical descriptors that can explain bioactivity variation within training inhibitors. Interestingly, two successful pharmacophores were selected within two statistically consistent QSAR models. The close similarity among the two binding models prompted us to merge them in a hybrid pharmacophore. The resulting model showed superior receiver operator characteristic curve (ROC) and closely resembled binding interactions seen in crystallographic ligand-PI3Kγ complexes. The resulting model was employed to screen the national cancer institute (NCI) list of compounds to search for new PI3Kγ ligands. After testing captured hits in vitro, 19 compounds showed nanomolar IC50 values against PI3Kγ. The chemical structures and purities of most potent hits were validated using NMR and MS experiments.

Discovery of new renin inhibitory leads via sequential pharmacophore modeling, QSAR analysis, in silico screening and in vitro evaluation.

The renin-angiotensin-aldosterone system is a major target for the clinical management of hypertension. Development of renin inhibitors has proven to be problematic due to poor bioavailability and complex synthesis. In this study, we combined pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent renin inhibitors employing 119 known renin ligands. Genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and physicochemical descriptors to yield self-consistent and predictive QSAR. Two binding pharmacophore models emerged in the optimal QSAR equation (r(96)(2)=0.746, F-statistic=43.552, r(LOO)(2)=0.697, r(PRESS)(2) against 23 test inhibitors=0.527). The successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve (ROC) profiles. The QSAR equations and their associated pharmacophore models were validated by the identification and experimental evaluation of new promising renin inhibitory leads retrieved from the National Cancer Institute (NCI) structural database. The most potent hits illustrated IC(50) value of 2.6 µM. Successful pharmacophore models were found to be comparable with crystallographically resolved renin binding pocket.