In Silico Molecular Docking and Dynamics Simulation Analysis of Potential Histone Lysine Methyl Transferase Inhibitors for Managing ß-Thalassemia.

A decreased hemoglobin synthesis is contemplated as a pathological indication of ß-thalassemia. Recent studies show that EPZ035544 from Epizyme could induce fetal hemoglobin (HbF) levels due to its proven capability to inhibit euchromatin histone lysine methyl transferase (EHMT2). Therefore, the development of EHMT2 inhibitors is considered promising in managing ß-thalassemia. Our strategy to find novel compounds that are EHMT2 inhibitors relies on the virtual screening of ligands that have a structural similarity to N2-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl) phenyl]-N4,6-dimethyl-pyrimidine-2,4-diamine (F80) using the PubChem database. In silico docking studies using Autodock Vina were employed to screen a library of 985 compounds and evaluate their binding ability with EHMT2. The selection of hit compounds was based on the docking score and mode of interaction with the protein. The top two ranked compounds were selected for further investigations, including pharmacokinetic properties analysis and molecular dynamics simulations (MDS). Based on the obtained docking score and interaction analysis, N-(4-methoxy-3-methylphenyl)-4,6-diphenylpyrimidin-2-amine (TP1) and 2-N-[4-methoxy-3-(5-methoxy-3H-indol-2-yl)phenyl]-4-N,6-dimethylpyrimidine-2,4-diamine (TP2) were found to be promising candidates, and TP1 exhibited better stability in the MDS study compared to TP2. In summary, our approach helps identify potential EHMT2 inhibitors, and further validation using in vitro and in vivo experiments could certainly enable this molecule to be used as a therapeutic drug in managing ß-thalassemia disease.

One-Pot Synthesis of Silver Nanoparticles Derived from Aqueous Leaf Extract of Ageratum conyzoides and Their Biological Efficacy.

The main objective of the present research work is to assess the biological properties of the aqueous plant extract (ACAE) synthesised silver nanoparticles from the herbal plant Ageratum conyzoides, and their biological applications. The silver nanoparticle syntheses from Ageratum conyzoides (Ac-AgNPs) were optimised with different parameters, such as pH (2, 4, 6, 8 and 10) and varied silver nitrate concentration (1 mM and 5 mM). Based on the UV-vis spectroscopy analysis of the synthesised silver nanoparticles, the concentration of 5 mM with the pH at 8 was recorded as the peak reduction at 400 nm; and these conditions were optimized were used for further studies. The results of the FE-SEM analysis recorded the size ranges (~30-90 nm), and irregular spherical and triangular shapes of the AC-AgNPs were captured. The characterization reports of the HR-TEM investigation of AC-AgNPs were also in line with the FE-SEM studies. The antibacterial efficacies of AC-AgNPs have revealed the maximum zone of inhibition against S. typhi to be within 20 mm. The in vitro antiplasmodial activity of AC-AgNPs is shown to have an effective antiplasmodial property (IC50:17.65 µg/mL), whereas AgNO3 has shown a minimum level of IC50: value 68.03 µg/mL, and the Ac-AE showed >100 µg/mL at 24 h of parasitaemia suppression. The α-amylase inhibitory properties of AC-AgNPs have revealed a maximum inhibition similar to the control Acarbose (IC50: 10.87 µg/mL). The antioxidant activity of the AC-AgNPs have revealed a better property (87.86% ± 0.56, 85.95% ± 1.02 and 90.11 ± 0.29%) when compared with the Ac-AE and standard in all the three different tests, such as DPPH, FRAP and H2O2 scavenging assay, respectively. The current research work might be a baseline for the future drug expansion process in the area of nano-drug design, and its applications also has a lot of economic viability and is a safer method in synthesising or producing silver nanoparticles.