In-Silico Selection of Wound-Healing Plant Secondary Molecules and Their Pro-Healing Activities on Experimental Models.

This study explored the potential of plant-derived molecules (PDMs) as a medicinal treatment for skin wounds. To assess their healing properties, 34 potential drug molecules (PDMs) and ten therapeutic targets were subjected to molecular docking and dynamics analysis, with allantoin used as a standard compound. Although aristolochic acid had the most potent inhibitory effect, its toxicity made it unsuitable for testing on cells and mice. Therefore, ß-caryophyllene (BC) and caryophyllene oxide (BCoxide) were chosen for further testing. The results showed that BC-treated HaCat cells had significantly improved scratch area closure, and both BC and BCoxide treatment produced positive effects such as reduced dermal cellularity and mast cells, decreased levels of inflammation markers IL-6 and TNF-α, and an increase in collagen deposition in mice tissues. However, these treatments did not accelerate wound healing. This study suggests that the PDMs selected based on in-silico results have significant potential for pro-healing abilities. It is essential to conduct further research to confirm our findings.

Synthesis, in silico, and in vivo anti-inflammatory evaluation of 3ß-cinnamoyloxy substituted pregna-4,16-diene-6,20-diones derivatives.

Pregnane derivatives have been studied mainly for their 5α-reductase activity. However, the anti-inflammatory activities of such compounds are still poorly explored. In the search for new anti-inflammatory agents, seven new pregnane derivatives 6a-g, with cinnamic acid esters at C-3 were prepared and fully characterized. The anti-inflammatory activity of compounds was assessed in TPA induced mice ear model. From them, compound 6 b was the most active to reduce edema, with an ED50 of 0.017 mg/ear. Also, Molecular Docking and Molecular Dynamics studies were performed to identify a potential molecular target related to the inflammatory process. The in vivo results suggest that 6 b could be a potent anti-inflammatory compound, while in silico studies suggest its interaction with some critical enzymes in the inflammatory response.

In silico hit optimization toward AKT inhibition: fragment-based approach, molecular docking and molecular dynamics study.

Protein kinase B also known as AKT is a cardinal node in different signaling pathways that regulates diverse cell processes. AKT has three isoforms that share high homology. Hyperactivation of each isoform is related with different types of cancer. This work describes the computational search for new inhibitors using a hit optimization process of the previously reported AKT pan inhibitor, a 2,4,6-trisubstituted pyridine. A database of new molecules was proposed using a variant of fragment-based docking methodology and previous reported considerations. Molecular docking followed by molecular dynamics studies were performed to select the best compounds and analyze their behavior. Protein-ligand complexes energy was calculated using molecular mechanics Poisson-Boltzmann surface area protocol. Further, proposed molecules were compared with the ChEMBL database of compounds assayed against AKT. Data analysis leads to determine the structural requirements necessary for a favorable interaction of the proposed ligands with the AKT pocket. Molecular dynamics data suggested that the pKa of the ligands is important for the stability in the AKT pocket. Molecular similarity analysis shows that proposed ligands have not been previously reported. Thus, ligands with high docking scores and favorable behavior on molecular dynamics simulations are proposed as potential AKT inhibitors.