New drug delivery systems for wound healing applications based on α/β/γ-cyclodextrin (α/β/γ-CD) acrylic (A) and styrenic (S) monomers have been synthesized and co-polymerized with 2-hydroxyethyl methacrylate (HEMA) via a cryo-polymerization technique.

The rapid and global propagation of the novel human coronavirus that causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of this virus. In this paper, we studied the spike protein S2 domain of SARS-CoV-2 as it is the most conserved component and controls the crucial fusion process of SARS-CoV-2 as a target for different databases of small organic compounds. Our in silico methodology, based on pharmacophore modeling, docking simulation and molecular dynamics simulations, was first validated with ADS-J1, a potent small-molecule HIV fusion inhibitor that has already proved effective in binding the HR1 domain and inhibiting the fusion core of SARS-CoV-1. It then focused on finding novel small molecules and new peptides as fusion inhibitors. Our methodology identified several small molecules and peptides as potential inhibitors of the fusion process. Among these, NF 023 hydrate (MolPort-006-822-583) is one of the best-scored compounds. Other compounds of interest are ZINC00097961973, Salvianolic acid, Thalassiolin A and marine_160925_88_2. Two interesting active peptides were also identified: AP00094 (Temporin A) and AVP1227 (GBVA5). The inhibition of the spike protein of SARS-CoV-2 is a valid target to inhibit the virus entry in human cells. The discussed compounds reported in this paper led to encouraging results for future in vitro tests against SARS-CoV-2.

In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are extensively available and routinely used for disease diagnosis. PET probes with peptide-based targeting are typically composed of small peptides especially developed to have high affinity and specificity for a range of cellular and tissue targets. These probes’ key benefits include being less expensive than traditional antibody-based PET tracers and having an effective chemical modification process that allows them to be radiolabeled with almost any radionuclide, making them highly appealing for clinical usage. Currently, as with every pharmaceutical design, the use of in silico strategies is steadily growing in this field, even though it is not part of the standard toolkit used during radiopharmaceutical design. This review describes the recent applications of computational design approaches in the design of novel peptide-based radiopharmaceuticals.

Precise binding free-energy predictions for ligands targeting metalloproteins, especially zinc-containing histone deacetylase (HDAC) enzymes, require specialized computational approaches due to the unique interactions at metal-binding sites. This study evaluates a docking algorithm optimized for zinc coordination to determine whether it could accurately differentiate between protonated and deprotonated states of hydroxamic acid ligands, a key functional group in HDAC inhibitors (HDACi). By systematically analyzing both protonation states, we sought to identify which state produces docking poses and binding energy estimates most closely aligned with experimental values. The docking algorithm was applied across HDAC 2, 4, and 8, comparing protonated and deprotonated ligand correlations to experimental data. The results demonstrate that the deprotonated state consistently yielded stronger correlations with experimental data, with R² values for deprotonated ligands outperforming protonated counterparts in all HDAC targets (average R² = 0.80 compared to the protonated form where R² = 0.67). These findings emphasize the significance of proper ligand protonation in molecular docking studies of zinc-binding enzymes, particularly HDACs, and suggest that deprotonation enhances predictive accuracy. The study’s methodology provides a robust foundation for improved virtual screening protocols to evaluate large ligand libraries efficiently. This approach supports the streamlined discovery of high-affinity, zinc-binding HDACi, advancing therapeutic exploration of metalloprotein targets. A comprehensive, step-by-step tutorial is provided to facilitate a thorough understanding of the methodology and enable reproducibility of the results.

Background: In melanoma, multiligand drug strategies to disrupt cancer-associated epigenetic alterations and angiogenesis are particularly promising. Here, a novel dual-ligand with a single shared pharmacophore capable of simultaneously targeting histone deacetylases (HDACs) and sigma receptors (σRs) was synthesized and subjected to phenotypic in vitro screening. Methods: Tumor cell proliferation and spreading were investigated using immortalized human cancer and normal cell lines. Angiogenesis was also evaluated in mouse endothelial cells using a tube formation assay. Results: The dual-ligand compound exhibited superior potency in suppressing both uveal and cutaneous melanoma cell viability compared to other cancer cell types or normal cells. Melanoma selectivity reflected inhibition of the HDAC-dependent epigenetic regulation of tumor proliferative kinetics, without involvement of σR signaling. In contrast, the bifunctional compound inhibited the formation of capillary-like structures, formed by endothelial cells, and tumor cell spreading through the specific regulation of σ₁R signaling, but not HDAC activity. Conclusions: Together, the present findings suggest that dual-targeted HDAC/σ₁R ligands might efficiently and simultaneously disrupt tumor growth, dissemination and angiogenesis in melanoma, a strategy amenable to future clinical applications in precision cancer treatment.

Cryogels are macroporous hydrogels prepared by cryo-gelation: a green technique that involves radical polymerization using water as a solvent