Revisiting the South Indian Traditional Plants against Several Targets of SARS-CoV-2 - An in silico Approach.

BACKGROUND: The south Indian Telugu states will celebrate a new year called 'Ugadi' which is a south Indian traditional festival. The ingredients used in ugadi pachadi have often also been used in food as well as traditional Ayurveda and Siddha medicinal preparations. Coronaviruses (CoVs) are a diverse family of enveloped positive-sense single-stranded RNA viruses which can infect humans and have the potential to cause large-scale outbreaks. OBJECTIVE: Considering the benefits of ugadi pachadi, we investigated the binding modes of various phytochemical constituents reported from its ingredients against five targets of SARS-CoV-2. METHODS: Flexible-ligand docking simulations were achieved through AutoDock version 1.5.6. Following 50ns of molecular dynamics simulation using GROMACS 2018.1 software and binding free energy (ΔGbind) of the protein-ligand complexes were calculated using the g_mmpbsa tool. ADME prediction was done using Qikprop of Schrodinger. RESULTS: From the molecular docking and MM/PBSA results compound Eriodictin exhibited the highest binding energy when complexed with nucleocapsid N protein (6M3M) (-6.8 kcal/mol, - 82.46 kJ/mol), bound SARS-CoV-2-hACE2 complex (6M0J) (-7.4 kcal/mol, -71.10 kJ/mol) and Mpro (6XR3) (-8.6 kcal/mol, -140.21 kJ/mol). Van der Waal and electrostatic energy terms highly favored total free energy binding. CONCLUSION: The compounds Eriodictin, Vitexin, Cycloart-3, 24, 27-triol, Agigenin, Mangiferin, Mangiferolic acid, Schaftoside, 27-Hydroxymangiferonic acid, Quercetin, Azadirachtol, Cubebin, Isomangiferin, Isoquercitrin, Malicarpin, Orientin and procyanidin dimer exhibited satisfactory binding energy values when compared with standard molecules. The further iterative optimization of high-ranked compounds following validation by in vitro and in vivo techniques assists in discovering therapeutic anti-SARS-CoV-2 molecules.

Biopharmaceutical insights of particulate emulsified systems - a prospective overview.

During the twenty-first century, drug discovery is expanding rapidly and a large number of chemical moieties are recognized. Many of them are poorly soluble and hence related biopharmaceutical constraints are to be addressed systematically. Among novel approaches to resolving biopharmaceutical issues, micro- and nano-emulsified systems serve as the best strategy for delivering both hydrophobic and hydrophilic drugs owing to their greater solubilization and transportation capabilities. Of late, the unique physical and biopharmaceutical properties of these liquid isotropic homogenous systems have gained substantive research importance. In addition nano/micro lipid systems share structural and functional similarity with that of the physiological lipids which offer better tolerance ability in the body. In this context, this article provides information on the historical emergence of particulate emulsified systems, importance and rationale of selection of carriers. It also encompasses the physicochemical principles that are responsible for the elevation of therapeutic outcomes of delivery systems. Detailed and schematic absorption of these drug delivery systems is explained here. Gastro-intestinal biochemistry necessary in the understanding of digestion process, lipolytic products formed, micellar structures, enzymes, transporters, mechanism of cell uptake involved after subsequent oral absorption are also emphasized. In addition, this article also explains disposition and pharmacokinetic properties of emulsified systems with real-time therapeutic research outcomes. The influence of biochemical compositions and biopharmaceutical principles on absorption and disposition patterns of ME/NEs was described in the article for the interest of readers and young researchers.

Synthesis and Pharmacological Evaluation of Acrylate-Based Gastrosparing NSAID Prodrugs.

Dexibuprofen and aceclofenac are well-known NSAID molecules, their oral use leads to gastrointestinal (GI) toxicity. To circumvent that GI toxicity, the prodrug approach is a better alternative. Hence, this research was undertaken to synthesize prodrugs of dexibuprofen and aceclofenac using acrylic polymers with degradable ester bonds. Dexibuprofen was linked to 2-hydroxypropyl methacrylate by an activated ester technique. The resulting material was copolymerized with 2-hydroxyethyl methacrylate and methyl methacrylate (in 1:3 mole ratios) by the free radical polymerization method, utilizing azoisobutyronitrile at 65-70°C. Similarly aceclofenac was also processed. The resulting prodrugs were characterized by IR, NMR, and elemental analysis. The synthesized prodrugs possess optimal physicochemical characteristics such as the intended molecular weight, lipophilicity, partition coefficient, and protein binding. The drug release on hydrolysis was studied in various fluids such as SGF (pH 1.2), SIF (pH 7.4), and SCF (pH 6.8), to establish the drug release kinetics. Pharmacological evaluation exhibited anti-inflammatory activity with remarkable reduction in ulcerogenicity compared to the parent drug. Under the conditions used, the prodrugs showed no antigenicity in Wistar rats. Thus, it was concluded that acrylic-based prodrugs were efficient in drug localization in the stomach, without gastric problems.