Punicalagin is the most bioactive pomegranate polyphenol with high antioxidant and free-radical scavenging activity and can potentially cure different ailments related to the cardiovascular system. The current research work was envisioned to predict the targeting efficiency of punicalagin (PG) nanoparticles to the macrophages, more specifically to bone marrow macrophages. For this, we selected mannose-decorated PLGA-punicalagin nanoparticles (Mn-PLGA-PG), and before formulating this nanocarrier in laboratory settings, we predicted the targeting efficiency of this nanocarrier by in silico analysis. The analysis proceeded with macrophage mannose receptors to be acquainted with the binding affinity and punicalagin-based nanocarrier interactions with this receptor. In silico docking studies of macrophage mannose receptors and punicalagin showed binding interactions on its surface. PG interacted with hydrogen bonds to the charged residue ASP668 and GLY666 and polar residue GLN760 of the Mn receptor. Mannose with a docking score of −5.811 Kcal/mol interacted with four hydrogen bonds and the mannose receptor of macrophage, and in PLGA, it showed a −4.334 Kcal/mol docking score. Further, the analysis proceeded with density functional theory analysis (DFT) and HOMO–LUMO analysis, followed by an extensive 100 ns molecular dynamics simulation to analyse the trajectories showing the slightest deviation and fluctuation. While analysing the ligand and protein interaction, a wonderful interaction was found among the atoms of the ligand and protein residues. This computational study confirms that this nanocarrier could be a promising lead molecule to regulate the incidence of drug-induced neutropenia. Furthermore, experimental validation is required before this can be stated with complete confidence or before human use.

Aromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL708 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates for therapeutic use in breast cancer.

: Human EGFR (epidermal growth factor receptor) family of tyrosine kinase receptors consists of four members, ErbB1-4. Abnormalities in the ErbB family characterize a variety of human cancers, including breast cancer. Tyrosine kinase is recruited by the activated EGFR cell surface receptor, which transmitted signals from the receptor to interact with intracellular signaling pathways and regulate cellular functions and biological processes. Targeting the intracellular signaling pathways has been aided in the drug development that was already in use and more continually being developed. The review article highlights the function of ErbB receptors/ligands, their role in signaling pathways, effective targeted drugs, and a combination of targeted drug strategies in the treatment of breast cancer that could be leading to the novel combination of anticancer drug delivery systems.

The present study divulges the consequences of lipidic nanoemulsions (cationized and non-cationized) on morphology and membrane integrity of Staphylococcus aureus using transmission electron microscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Transmission electron microscopic (TEM) images reveal that the cationized lipidic emulsions (CLEs) remained adhered even after the hostile treatment to remove nanoemulsions by centrifugation owing to electrostatic attraction between CLE and negatively charged bacterial surface. TEM images portray the extensive cell lyses owing to the release of cytoplasmic content when treated with both CLE and Non-CLE (NCLE). The AFM analysis of the NCLE and CLE treated S. aureus cells showed the root mean square roughness of 11.3 ± 2.8 nm and 17.7 ± 3.2 nm, respectively. The complete losses of bacterial colonies after 45 min of contact with NCLE were observed. No viable bacterial colonies were noticeable after 10 min of contact when treated with CLE, indicating better rate of killing with respect to NCLE. Similar results were obtained in the zone of inhibition studies. Significant (p < 0.05) increase of cytoplasmic material was observed both in NCLE (0.192 ± 0.003) and CLE (0.308 ± 0.012) as compared to control (0.019 ± 0.002). The present finding illustrates that the NCLE and CLE had caused significant membrane disorganization leading to release of cytoplasmic content causing irreversible cell damage, which is in accordance with the TEM, SEM and AFM studies.