The hunt for anti-browning agents in the food and agricultural industries aims to minimize nutritional loss and prolong post harvest storage. In the present study, the effect of cyanidin-3-sophoroside (CS) from Garcinia mangostana rind, on polyphenol oxidase (PPO) activity was investigated. The non-competitive inhibition mode of CS was determined by Lineweaver Burk plot. CS forms a ground-state complex by quenching the intrinsic fluorescence of PPO. The static quenching was temperature-dependent with an activation energy of 4.654 ± 0.1091 kJ mol−1 to withstand the disruption of amino acid residues of the enzyme binding site. The enzyme conformational change was validated by 3D fluorescence and CD spectrum. Docking (binding energy −8.124 kcal/mol) and simulation studies confirmed the binding pattern and stability. CS decreased PPO activity and browning index of fresh cut apples and prolonged the shelf life. Thus, CS appears to be a promising anti-browning agent to control enzymatic browning. © 2017 Elsevier Ltd

George Priya Doss C

Department of Integrative Biology

School of Bio Sciences and Technology

Vellore Campus

Siva R

Department of Biotechnology

Hemachandran H

Anantharaman A

Mohan S

Mohan G

Kumar D.T

Dey D

Kumar D

Dey P

Choudhury A

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Food Chemistry

Bixin and crocin are natural apocarotenoids utilized as food colorants and additives in food industries worldwide. For safety assessment, it is necessary to understand the biological interaction of food colorants. In our present study, we report the interaction of two apocarotenoids with bovine serum albumin (BSA) at physiological pH using spectroscopic techniques and in silico tools. The binding constant and the mode of binding sites have been studied. The enthalpic and entropic contribution to the intermolecular binding event was analyzed and it was found that the contribution of hydrogen bonding and hydrophobic interactions was dominant. The adverse temperature dependence in the unusual static quenching is found to b. reasonable consequence of the large activation energy requirement in the binding process, which is required to overcome the fundamental block and i. direct result of the unique microstructure of the binding sites. To confirm the experimental analysis, we investigated the binding patterns using different in silico tools. combination of molecular docking, molecular dynamics, and toxicity analysis was performed, and the obtained results revealed that both the apocarotenoids had high binding affinity wit. binding energy of −5.44 and −5.93 kcal/mol for bixin and crocin, respectively, with no toxic effects and are in accordance with our experimental analysis. The results directly revealed the flexibility of the protein toward bixin and crocin which ha. great impact on the interaction. Thus bixin and crocin can guardedly be used as food colorants in food industries. © 2017 Informa UK Limited, trading as Taylor &amp; Francis Group.

Journal of Biomolecular Structure and Dynamics

Structural insights into the binding mode and conformational changes of BSA induced by bixin and crocin

Klebsiella pneumoniae, BA6753 was cultured from a patient in the Clinical Microbiology Laboratory of Christian Medical College. K. pneumoniae, BA6753 has a multidrug resistance plasmid encoding novel FosA variant-7, fosfomycin resistance enzyme. Minimal side effects and a wide range of bactericidal activity of fosfomycin have resulted in its expanded clinical use that prompts the rise of fosfomycin-resistant strains. At present, there are no effective inhibitors available to conflict the FosA-medicated fosfomycin resistance. To develop effective FosA inhibitors, it is crucial to understand the structural and dynamic properties of resistance enzymes. Hence, the present study focuses on the identification of potent inhibitors that can effectively bind to the fosfomycin resistance enzyme, thus predispose the target to inactivate by the second antibiotic. Initially, a series of active compounds were screened against the resistant enzyme, and the binding affinities were confirmed using docking simulation analysis. For efficient activity, the binding affinity of the resistance enzyme ought to be high with the inhibitor than the fosfomycin drug. Consequently, the enzyme-ligand complex which showed higher binding affinity than the fosfomycin was employed for subsequent analysis. The stability of the top scoring enzyme-ligand complex was further validated using molecular dynamics simulation studies. On the whole, we presume that the compound 19583672 demonstrates a higher binding affinity for the resistance enzyme comparing to other compounds and fosfomycin. We believe that further enhancement of the lead compound can serve as a potential inhibitor against resistance enzyme in drug discovery process. J. Cell. Biochem. 118: 4088–4094, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Journal of Cellular Biochemistry

A Molecular Docking and Dynamics Approach to Screen Potent Inhibitors Against Fosfomycin Resistant Enzyme in Clinical Klebsiella pneumoniae

Excessive melanin production leads to hyperpigmentation disorders which results in distressing aesthetic values. Though there are some synthetic depigmentation agents available it has been reported to possess cytotoxic and mutagenic effects. Hence there is a need for the development of safe and non toxic natural tyrosinase inhibitors. Here we report the role of santalin, the chief constituent of Pterocarpus santalinus in inhibition of tyrosinase and melanin synthesis. Santalin inhibited tyrosinase activity dose dependently. Inhibitory kinetic studies revealed mixed type of inhibition with reversible mechanism. Santalin was found to interact with the fluorophore amino acid residue of tyrosinase. Analysis of circular dichroism spectra showed the binding of santalin to tyrosinase which induced the loss of secondary helical structure. Molecular docking result suggested that santalin interact with the catalytic core of tyrosinase through strong hydrogen and hydrophobic bonding. The results of in vitro studies showed santalin inhibited melanogenesis through down regulation of MITF, tyrosinase, TRP-1 and TRP-2 without any cytotoxic effects towards B16F0 melanoma cells. Therefore, our results suggested that santalin possesses anti-tyrosinase activity, which could be utilized as a safe depigmentation agent in the cosmetic field for the treatment of hyperpigmentation disorder. © 2016 Elsevier B.V.

International Journal of Biological Macromolecules

Functionality study of santalin as tyrosinase inhibitor: A potential depigmentation agent

The main aim of the current study is to explore the bioactive potential of Streptomyces sp. VITJS8 isolated from the marine saltern. The cultural, biochemical, and morphological studies were performed to acquire the characteristic features of the potent isolate VITJS8. The 16Sr DNA sequencing was performed to investigate the phylogenetic relationship between the Streptomyces genera. The structure of the compound was elucidated by gas chromatography-mass spectrometry (GC-MS), infra-red (IR), and ultra-violet (UV) spectroscopic data analysis. The GC-MS showed the retention time at 22.39 with a single peak indicating the purity of the active compound, and the molecular formula was established as C14H9ONCl2 based on the peak at m/z 277 [M]+. Furthermore, separated by high-performance liquid chromatography (HPLC), their retention time (tr) 2.761 was observed with the absorption maxima at 310 nm. The active compound showed effective inhibitory potential against four clinical pathogens at 500 μg/mL. The antioxidant activity was found effective at the IC50 value of 500 μg/mL with 90 % inhibition. The 3-(4,5-dimethylthiazol-2-yl)-2,5-ditetrazolium bromide (MTT) assay revealed the cytotoxicity against HepG2 cells at IC50 of 250 μg/mL. The progression of apoptosis was evidenced by morphological changes by nuclear staining. The DNA fragmentation pattern was observed at 250 μg/mL concentration. Based on flow cytometric analysis, it was evident that the compound was effective in inhibiting the sub-G0/G1 phase of cell cycle. The in vitro findings were also supported by the binding mode molecular docking studies. The active compound revealed minimum binding energy of −7.84 and showed good affinity towards the active region of topoisomerase-2α that could be considered as a suitable inhibitor. Lastly, we performed 30 ns molecular dynamic simulation analysis using GROMACS to aid in better designing of anticancer drugs. Simulation result of root mean square deviation (RMSD) analysis showed that protein-ligand complex reaches equilibration state around 10 ns that illustrates the docked complex is stable. We propose the possible mechanism of sesquiterpenes to play a significant role in antitumor cascade. Hence, our studies open up a new facet for a potent drug as an anticancer agent. © 2015, Springer-Verlag Berlin Heidelberg.

Applied Microbiology and Biotechnology

Binding and molecular dynamic studies of sesquiterpenes (2R-acetoxymethyl-1,3,3-trimethyl-4t-(3-methyl-2-buten-1-yl)-1t-cyclohexanol) derived from marine Streptomyces sp. VITJS8 as potential anticancer agent

In this present study, the inhibitory mechanism of three selected apocarotenoids (bixin, norbixin and crocin) on the diphenolase activity of tyrosinase has been investigated. The preliminary screening results indicated that apocarotenoids inhibited tyrosinase activity in a dose-dependent manner. Kinetic analysis revealed that apocarotenoids reversibly inhibited tyrosinase activity. Analysis of fluorescence spectra showed that apocarotenoids quenched the intrinsic fluorescence intensity of the tyrosinase. Further, molecular docking results implied that apocarotenoids were allosterically bound to tyrosinase through hydrophobic interactions. The results of the in vitro studies suggested that higher concentrations of bixin and norbixin inhibited tyrosinase activity in B16F0 melanoma cells. Our results suggested that apocarotenoids could form the basis for the design of novel tyrosinase inhibitors. © 2015 The Society for Biotechnology, Japan.

Journal of Bioscience and Bioengineering

Inhibitory effect of apocarotenoids on the activity of tyrosinase: Multi-spectroscopic and docking studies

Bixin and norbixin are natural food colourants synthesised from Bixa orellana L seeds. This study explores the mechanism of apocarotenoids (bixin and norbixin) on the aggressive B16 murine melanoma as an anti-cancer agent. The apocarotenoids inhibited the cell viability of B16 melanoma in a time- and concentration-dependent manner. Apocarotenoids markedly induced cell morphology change, nuclear condensation, DNA fragmentation, and mitochondrial dysfunction through the depletion of glutathione activity, and also induced reactive oxygen species (ROS) generation. Furthermore, apocarotenoids effectively enhanced sub-G1 population and also activated caspase 9 and caspase 3 activities. It decreased and increased the gene expression of the microphthalmia-associated transcription factor, anti-apoptotic Bcl-2 and pro-apoptotic Bax, respectively. Furthermore, molecular docking studies revealed that apocarotenoids inhibited anti-apoptotic protein (Bcl-2 and Bcl-XL) through hydrophobic interaction. These findings suggest that bixin and norbixin act as a promising chemotherapeutic agent against melanoma by inducing apoptosis through mitochondrial-associated death pathway. © 2015 Elsevier Ltd.

Journal of Functional Foods

Induction of apoptosis by apocarotenoids in B16 melanoma cells through ROS-mediated mitochondrial-dependent pathway

In our present study, the inhibitory effect of brazilein from Caesalpinia sappan on tyrosinase activity was investigated through multi-spectroscopic and molecular docking techniques. The result has shown that brazilein reversibly inhibited tyrosinase in a mixed type manner. The interaction of brazilein with the amino acid residues of tyrosinase has been validated through fluorescence quenching studies. Copper interaction studies suggested that brazilein could bind with copper ions of the enzyme. Circular dichroism analysis confirmed that brazilein induced secondary structural changes in tyrosinase. Docking studies further authenticate that brazilein forms hydrophobic and hydrogen bonding with the active site residues of tyrosinase. Moreover, in vitro studies confirmed that the inhibitory mechanism of cellular tyrosinase and melanin synthesis by brazilein in B16F0 melanoma cells. These results suggested that brazilein act as a potential tyrosinase inhibitor and it would contribute as a of novel tyrosinase inhibitor in food, cosmetic and pharmaceutical industry.

Journal	Data powered by TypesetFood Chemistry
Publisher	Data powered by TypesetElsevier BV
ISSN	0308-8146
Open Access	No