Bioevaluation and molecular docking analysis of novel phenylpropanoid derivatives as potent food preservative and anti-microbials.

Novel derivatives were synthesized using natural scaffold, like phenylpropanoids C6-C3 backbone to reduce unfavorable browning of food due to tyrosinase and oxidative spoilage. Most of the compounds displayed mushroom tyrosinase inhibition better than kojic acid. Compound CE48 exhibited better anti-tyrosinase (IC50-29.64 µM) and antioxidant (EC50-12.67 µM) activity than the reference compounds, kojic acid (IC50-50.30 µM) and ascorbic acid (EC50-14.55 µM), respectively. Compounds SAM30, SE78, 11F, and CE48 showed better anti-B. subtilis, anti-S. aureus, and anti-A. niger activity, respectively, compared to their parents. Molecular docking studies between inhibitors and mushroom tyrosinase corroborated the experimental reports, except SAM30 (glide score - 8.117) and SE78 (glide score - 6.151). In silico absorption, distribution, metabolism, excretion/toxicity (ADME/T) and toxicological studies of these newly synthesized compounds exhibited acceptable pharmacokinetic and safety profiles, like good aqueous solubility (- 3.34 to - 7.57), low human oral absorption (e.g., SAM30, SE78, FAM34), low gut-blood barrier permeability [36.67-209.88 nm/s in Cancer coli-2 (Caco-2) cells] and [19.45-91.51 nm/s in Madin-Darby Canine Kidney (MDCK) cells], low blood-brain barrier penetration, non-mutagenicity, and non-carcinogenicity. Interestingly, the synthesized compounds also possessed multifunctional properties, like microbial growth inhibitor, free radicals scavenger, and it also prevented browning of raw fruits and vegetables by inhibiting tyrosinase enzyme. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02636-0.

Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors.

BACKGROUND: Infections caused by microorganisms are the major cause of death today. The tremendous and improper use of antimicrobial agents leads to antimicrobial resistance. AIM AND OBJECTIVE: Various currently available antimicrobial drugs are inadequate to control the infections and lead to various adverse drug reactions. Efforts based on computer-aided drug design (CADD) can excavate a large number of databases to generate new, potent hits and minimize the requirement of time as well as money for the discovery of newer antimicrobials. Pharmaceutical sciences also have made development with advances in drug designing concepts. The current research article focuses on the study of various G-6-P synthase inhibitors from literature cited molecular database. Docking analysis was conducted and ADMET data of various molecules was evaluated by Schrodinger Glide and PreADMET software, respectively. Here, the results presented efficacy of various inhibitors towards enzyme G-6-P synthase. Docking scores, binding energy and ADMET data of various molecules showed good inhibitory potential toward G-6-P synthase as compared to standard antibiotics. This novel antimicrobial drug target G-6-P synthase has not so extensively been explored for its application in antimicrobial therapy, so the work done so far proved highly essential. This article has helped the drug researchers and scientists to intensively explore about this wonderful antimicrobial drug target. MATERIALS AND METHODS: The Schrodinger, Inc. (New York, USA) software was utilized to carry out the computational calculations and docking studies. The hardware configuration was Intel® core (TM) i5-4210U CPU @ 2.40GHz, RAM memory 4.0 GB under 64-bit window operating system. The ADMET data was calculated by using the PreADMET tool (PreADMET ver. 2.0). All the computational work was completed in the Laboratory for Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D. University, Rohtak, INDIA. RESULTS: Molecular docking studies were carried out to identify the binding affinities and interaction between the inhibitors and the target proteins (G-6-P synthase) by using Glide software (Schrodinger Inc. U.S.A.-Maestro version 10.2). Grid-based Ligand Docking with Energetic (Glide) is one of the most accurate docking softwares available for ligand-protein, protein-protein binding studies. A library of hundreds of available ligands was docked against targeted proteins G-6-P synthase having PDB ID 1moq. Results of docking are shown in Table 1 and Table 2. Results of G-6-P synthase docking showed that some compounds were found to have comparable docking score and binding energy (kj/mol) as compared to standard antibiotics. Many of the ligands showed hydrogen bond interaction, hydrophobic interactions, electrostatic interactions, ionic interactions and π- π stacking with the various amino acid residues in the binding pockets of G-6-P synthase. CONCLUSION: The docking study estimated free energy of binding, binding pose andglide score and all these parameters provide a promising tool for the discovery of new potent natural inhibitors of G-6-P synthase. These G-6-P synthase inhibitors could further be used as antimicrobials. Here, a detailed binding analysis and new insights of inhibitors from various classes of molecules were docked in binding cavity of G-6-P synthase. ADME and toxicity prediction of these compounds will further accentuate us to study these compounds in vivo. This information will possibly present further expansion of effective antimicrobials against several microbial infections.

In vitro evaluation of antimicrobial activity of Kutajghan vati - an Ayurvedic formulation.

The present investigation focuses to determine the antimicrobial potential of an Ayurvedic formulation Kutajghan vati. In this study the activity of this formulation was compared with the standard antibiotics like Amikacin and Norfloxacin. Ethanol, methanol and acetone extract of Kutajghan vati demonstrated good antimicrobial activity and thus can form the basis for the development of a novel antibacterial formulation.