Exploring Type II Diabetes Inhibitors from Genus Daphne Plant-species: An Integrated Computational Study.

BACKGROUND: Plant species of the genus Daphne clasps a historical background with a potential source of bioactive phytochemicals such as flavonoids and daphnodorins. These compounds manifest a significant chemotaxonomic value in drug discovery. Their flair comprehensive pharmacological, phytochemical, biological, catalytic, and clinical utilities make them exclusively unique. This study was conducted to investigate the optimization and structure-based virtual screening of these peculiar analogs. The majority of the active constituents of medicines are obtained from natural products. Previously, before the invention of virtual screening methods or techniques, almost 80% of drugs were obtained from natural resources. Comparing reported data to drug discovery from 1981 to 2007 signifies that half of the FDA-approved drugs are obtained from natural resources. It has been reported that structures of natural products that have particularities of structural diversity, biochemical specification, and molecular properties make them suitable products for drug discovery. These products basically have unique chiral centers which increase their structural complexity than the synthesized drugs. METHOD: This work aimed to probe the use of daphnodorins analogs for the first time as antidiabetic inhibitors based on significant features and to determine the potential of daphnodorin analogs as antidiabetic inhibitors through computational analysis and structure-based virtual screening. A dataset of 38 compounds was selected from different databases, including PubChem and ZINC, for computational analysis, and optimized compounds were docked against various co-crystallized structures of inhibitors, antagonists, and receptors which were downloaded from PDB by using AutoDock Vina (by employing Broyden-Fletcher-Goldfarb-Shanno method), Discovery studio visualizer 2020, PYMOL (Schrodinger). Docking results were further validated by Molecular dynamic simulation and MM-GBSA calculation. Quantitative structure-activity relationship (QSAR) was reported by using Gaussian 09W by intimating Density Functional Theory (DFT). Using this combination of multi-approach computational strategy, 14 compounds were selected as potential exclusive lead compounds, which were analyzed through ADMET studies to pin down their druglike properties and toxicity. RESULT: At significant phases of drug design approaches regular use of molecular docking has helped to promote the separation of important representatives from 38 pharmaceutically active compounds by setting a threshold docking score of -9.0 kcal/mol which was used for their exposition. Subsequently, by employing a threshold it was recognized that 14 compounds proclaimed this threshold for antidiabetic activity. Further, molecular dynamic simulation, MM-GBSA, ADMET, and DFT results screened out daphnegiralin B4 (36) as a potential lead compound for developing antidiabetic agents. CONCLUSION: Our analysis took us to the conclusion that daphnegiralin B4 (36) among all ligands comes out to be a lead compound having drug-like properties among 38 ligands being non-carcinogenic and non-cytotoxic which would benefit the medical community by providing significant drugs against diabetes. Pragmatic laboratory investigations identified a new precursor to open new doors for new drug discovery.

Plant-Based Bioactive Phthalates Derived from Hibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition.

Hibiscus rosa-sinensis is an attractive, ever-blossoming, and effortlessly available plant around the globe. The fabulous flowers of H. rosa-sinensis enjoy a significant status in folk medicine throughout the world and comprise a range of phyto constituents due to which this splendid flower owns numerous biological and pharmaceutical activities like antioxidant, antifungal, antimicrobial, anti-inflammatory, antipyretic, antidiabetic, and antifertility activity. Considering this, column chromatographic isolation of the phytoconstituents of ethyl acetate fraction of the flowers of H. rosa-sinensis was performed. A series of five phthalates including Di-n-octyl phthalate (HR1), ditridecyl phthalate (HR2), 1-allyl 2-ethyl phthalate (HR3), diethyl phthalate (HR4), and bis (6-methylheptyl) phthalate (HR5) were isolated. The structures of the isolated phthalates were elucidated by gas chromatography-mass spectrometry, 1H NMR, and 13C NMR. In silico and in vitro antidiabetic and antioxidant potential and DFT studies of isolated phthalates were carried out. In our study, isolated ligands were explored as potent antidiabetic as well as antioxidant agents as they exhibited good binding affinity (in in vitro and in silico experiments) against all selected protein targets. Compounds HR1-HR5 showed that the binding affinity value ranged from -5.9 to -5.2 kcal/mol, -5.5 to -4.3 kcal/mol, and -5.0 to -4.1 kcal/mol for target proteins 1HNY, 2I3Y, and 5O40, respectively. Among all isolated phthalates, HR5 can be a lead compound as it showed the best binding affinity with human pancreatic α-amylase (ΔG = -5.9 kcal/mol) and displayed a minimum inhibition concentration (IC50) of 11.69 µM among all phthalates. Compound HR1 was the best docked and scored compound for inhibiting glutathione peroxidase; however, HR2 possessed the lowest binding score of -5.0 kcal/mol, thus indicating the highest potential among isolated phthalates for inhibiting the superoxide dismutase. Furthermore, the top-ranked docked ligand-protein complex for each protein was assessed for stability of protein and complex mobility by molecular dynamics simulation using the IMOD server.

Risk Assessment of Hepatocellular Carcinoma with Aflatoxin B1 Exposure in Edible Oils.

Contamination of edible oils with aflatoxins (AFs) is a universal issue due to the detrimental effects of aflatoxins on human health and the fact that edible oils are a major source of fungal growth, particularly storage fungi (Aspergillus sp.). The objective of this study was to assess aflatoxin B1 (AFB1) in edible oil used in fried food in order to determine the risk of cancer from AFB1 exposure through cooked food using the FAO/WHO's and EFSA's margin of exposure (MOE) quantitative liver cancer risk approaches. Using Mycosep 226 columns and HPLC-FLD, 100 samples of cooking oils (soybean, canola, and sunflower oil) from different food points were analyzed for contamination with aflatoxins. Of all the samples tested, 89% were positive for total aflatoxins and AFB1, with 65% indicating AF concentrations beyond permitted levels. Canola oil was found to contain higher levels of AFB1 and AFs than soybean and sunflower oil. Almost 71 percent of canola oil samples (range of 54.4-281.1 µg/kg) were contaminated with AF levels higher than the proposed limits of the European Union (20 µg/kg). The consumption of canola oil samples used in fried foods had MOE values that were significantly lower as compared to sunflower and soybean oils, indicating that risk reduction is feasible. Additionally, compared to soybean and sunflower oil, canola oil exhibited a greater threat of liver cancer cases linked to AFB1 exposure (17.13 per 100,000 males over 35 and 10.93 per 100,000 females over 35). Using a quantitative liver cancer approach, health risk valuation demonstrated that males and females over the age of 35 are at significant risk of developing liver cancer. The health risk assessment exposed that the males and female over the age of 35 are at considerable risk of liver cancer by using a quantitative liver cancer approach. The innovation of this study lies in the fact that no such study is reported related to liver cancer risk evaluation accompanied with AFB1 exposure from consumed edible oil. As a result, a national strategy must be developed to solve this problem so that edible oil products are subjected to severe regulatory examination.

Synthesis and characterization of hydroxyethyl cellulose copolymer modified polyurethane bionanocomposites.

Bio based polyurethane nanocomposites (renewable thermosets) show a diverse range in properties, processing components and production of smart materials for health, food, and energy sectors. In this work, polyurethane nanocomposites based on isophorone diisocyanate (IPDI), and hydroxyl terminated-polybutadiene (HTPB) incorporating clay were modified using hydroxyethyl cellulose (HLAC) to be further assessed for thermal and mechanical properties. Elastomers samples were prepared by blending clay suspension and PU prepolymer to attain clay contents of 0.3, 0.5, and 1% (weight on dry basis) along with butane diol and HLAC chain extenders. Effect of nanofiller aggregation and dispersion on the thermal degradation and surface morphology of the bionanocomposites were studied. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy/energy dispersive X-ray (SEM/EDX) and thermal gravimetric (TG) techniques were used to investigate the interactions among PU matrix, clay nanofillers, and HLAC. Mechanical testing indicated an increase in tensile strength and a decrease in elongation at break (%) by just adding 0.3 wt% clay. The thermal stability of the bionanocomposites was improved with the addition of clay. The results of the thermal and mechanical studies demonstrated the feasibility of the bionanocomposites as strong and thermally stable elastomers with low filler loading.

Polyhydroxyalkanoates: Next generation natural biomolecules and a solution for the world's future economy.

Petrochemical plastics have become a cause of pollution for decades and finding alternative plastics that are environmental friendly. Polyhydroxyalkanoate (PHA), a biopolyester produced by microbial cells, has characteristics (biocompatible, biodegradable, non-toxic) that make it appropriate as a biodegradable plastic substance. The different forms of PHA make it suitable to a wide choice of products, from packaging materials to biomedical applications. The major challenge in commercialization of PHA is the cost of manufacturing. There are a lot of factors that could affect the efficiency of a development method. The development of new strategic parameters for better synthesis, including consumption of low cost carbon substrates, genetic modification of PHA-producing strains, and fermentational strategies are discussed. Recently, many efforts have been made to develop a method for the cost-effective production of PHAs. The isolation, analysis as well as characterization of PHAs are significant factors for any developmental process. Due to the biodegradable and biocompatible properties of PHAs, they are majorly used in biomedical applications such as vascular grafting, heart tissue engineering, skin tissue repairing, liver tissue engineering, nerve tissue engineering, bone tissue engineering, cartilage tissue engineering and therapeutic carrier. The emerging and interesting area of research is the development of self-healing biopolymer that could significantly broaden the operational life and protection of the polymeric materials for a broad range of uses. Biodegradable and biocompatible polymers are considered as the green materials in place of petroleum-based plastics in the future.

Synthesis and characterization of graphene nanoplatelets-hydroxyethyl cellulose copolymer-based polyurethane bionanocomposite system.

Bionanocomposites is an emerging class of biohybrid materials, have a significant impact in environmental and biomedical fields owing to their high performance, lightweight, unique, and ecofriendly properties. A major challenge in the multiphase bionanocomposites system is to subtle control over the performance by managing the individual properties of reacting components. Herein, we presented the preliminary investigation on bionanocomposite system based on graphene nanoplatelets (GNPs) and hydroxyethyl cellulose graft poly(lactic acid) copolymer-polyurethane (HLAC-PU) with the aim to understand the structure property correlation for proposed applications in electronics and medical areas. The HLAC was fabricated by graft copolymerization of hydroxyethyl cellulose (HEC) and lactic acid (LA) with dibutyltin dilaurate. The HLAC was used to get a bio-functionalized PU matrix reinforced with GNPs by step-growth polymerization method. The structural, surface, and thermal properties of the HLAC and GNPs-HLAC-PU bionanocomposites were studied. The spectroscopic techniques confirmed the structure of bionanocomposites by the identification of related bands. The SEM/EDX results demonstrated that the 0.3 wt% of GNPs dispersed well in the HLAC-PU matrix and offered higher crystallinity. The reinforcement of the 0.3 wt% of GNPs has meaningfully enhanced the thermal stability producing higher residue contents. The reinforced GNPs filler increased the water resistance of bionanocomposites by reducing their water vapor permeability.

Preparation of hydroxyethyl cellulose/halloysite nanotubes graft polylactic acid-based polyurethane bionanocomposites.

2-Hydroxyethyl cellulose graft polylactic acid copolymer (HLAC) was prepared by graft copolymerization of lactic acid (LA) and 2-hydroxyethyl cellulose (2-HEC), initiated by dibutyltin dilaurate (DBTDL) catalyst in aqueous media. Halloysite nanotubes (HNTs)/polyurethane (PU) bionanocomposites were prepared using the HLAC as chain extender in the step-growth polymerization. HNTs were dispersed in HLAC based PU matrix at different weight ratios of 0.30, 0.50, 1.00, and 3.00. Chemical structure and morphology of the graft copolymer and bionanocomposite elastomers were characterized using solid state 1H NMR, ATR-FTIR, XRD, and SEM-EDX, while thermal degradation behavior was studied by TGA and DSC techniques. Surface morphology of the HNTs reinforced HLAC/PU bio-nanocomposites demonstrated the homogeneous dispersion of HNTs with little wavy rough surface at low contents which turned to be brittle at higher contents due to agglomerated HNTs. It is observed that the lower contents of HNTs were completely exfoliated in the HLAC/PU matrix. Crystalline pattern of the elastomers improved at lower contents of HNTs that enhanced the thermal stability of the bionanocomposites. The mechanical testing suggested that HNTs/HLAC/PU bionanocomposites have higher values of tensile strength and % elongation with only 0.3-0.5 wt% contents of HNTs that suggested the potential applications of elastomers at economic cost.

A review on versatile applications of blends and composites of pullulan with natural and synthetic polymers.

Pullulan is a non-ionic, linear, water-soluble and a neutral polysaccharide. It is composed of α-(1,6) repeated maltotriose units via α-(1,4) glycosidic bond having chemical formula (C6H10O5)n. It shows non-immunogenic, non-toxic, non-carcinogenic and non-mutagenic properties. It is used in food edible coatings, films, as flocculant, foaming agent and adhesive. It may also be used as a carrier for bioactive compounds and a protective packaging for food and pharmaceutical products. Therefore, it is blended with different polymers such as carrageenan, mucilages, chitosan, cellulose, sodium alginate, starch, polyethyleneimine, whey-protein, polyisopropylacrylamide, histone, jeffamine, polyamidoamine, pemulen, hyaluronic acid, polyvinyl alcohol and caboxymethyl cellulose. In this article, a comprehensive overview of combination of pullulan with natural and synthetic polymers and their applications in biomedical field involving drug delivery system, tissue engineering, wound healing and gene therapy, is presented. It also describes the utilization of pullulan based materials in food industry, water treatment and pharmaceutical industry. All the technical scientific issues have been addressed; highlighting the recent advancements.

Pectins functionalized biomaterials; a new viable approach for biomedical applications: A review.

Pectins are natural complex heteropolysaccharides, composed of (1, 4)-linked α-d-galacturonic acid residues and variety of neutral sugars such as rhamnose, galactose and arabinose. It is second most abundant component of the cell wall of all land plants. It has wide applications in various fields due to its use as gelling, emulsifying or stabilizing agent and as well as its non-toxic, biocompatible and biodegradable nature. Considering these versatile properties this review sheds a light on the synthesis, modification, characterization and applications of pectin based polymers. Most of them are used in industries, pharmaceutics, nutraceutics, drug delivery, tissue engineering, food packaging and cosmetics. Properties of pectin can be improved and modified by forming derivatives, blends and composites.