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      Integration of in vitro and in silico perspectives to explain chemical characterization, biological potential and anticancer effects of Hypericum salsugineum: A pharmacologically active source for functional drug formulations

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          Abstract

          The genus Hypericum is one of the most popular genera in both traditional medicine and scientific platform. This study is designed to provide conceptual insights on the biological potential and chemical characterization of H. salsugineum, which is endemic to Turkey. The qualitative and quantitative phenolic content of the extracts was characterized by HPLC-ESI-MS n. Biological efficiency was investigated by enzyme inhibitory assays (cholinesterases, tyrosinase, amylase, and glucosidase) and anti-cancer efficacy tests (anti-proliferative activities with the iCELLigence technology, colony formation and wound healing scratch assays). Phenolic acids (3- O-caffeoylquinic, 5- O-caffeoylquinic, and 4- O-caffeoylquinic acids) were the predominant group in the studied extracts, although several flavonoids were also detected and quantified. The extracts exhibited good inhibitory effects on tyrosinase and glucosidase, while they had weak ability against cholinesterases and amylase. Computational studies were also performed to explain the interactions between the major phenolics and these enzymes. The extracts displayed significant anti-cancer effects on breast carcinoma cell lines. Our findings suggest that Hypericum salsugineum could be valued as a potential source of biologically-active compounds for designing novel products.

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          Choosing the right cell line for breast cancer research

          Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research.
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            Epik: a software program for pK( a ) prediction and protonation state generation for drug-like molecules.

            Epik is a computer program for predicting pK(a) values for drug-like molecules. Epik can use this capability in combination with technology for tautomerization to adjust the protonation state of small drug-like molecules to automatically generate one or more of the most probable forms for use in further molecular modeling studies. Many medicinal chemicals can exchange protons with their environment, resulting in various ionization and tautomeric states, collectively known as protonation states. The protonation state of a drug can affect its solubility and membrane permeability. In modeling, the protonation state of a ligand will also affect which conformations are predicted for the molecule, as well as predictions for binding modes and ligand affinities based upon protein-ligand interactions. Despite the importance of the protonation state, many databases of candidate molecules used in drug development do not store reliable information on the most probable protonation states. Epik is sufficiently rapid and accurate to process large databases of drug-like molecules to provide this information. Several new technologies are employed. Extensions to the well-established Hammett and Taft approaches are used for pK(a) prediction, namely, mesomer standardization, charge cancellation, and charge spreading to make the predicted results reflect the nature of the molecule itself rather just for the particular Lewis structure used on input. In addition, a new iterative technology for generating, ranking and culling the generated protonation states is employed.
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              α-glucosidase inhibitors from plants: A natural approach to treat diabetes

              Diabetes is a common metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as diabetic neuropathy, retinopathy, and cardiovascular diseases. One of the effective managements of diabetes mellitus, in particular, non–insulin-dependent diabetes mellitus (NIDDM) to decrease postprandial hyperglycemia, is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase, in the digestive organs. α-Glucosidase is the key enzyme catalyzing the final step in the digestive process of carbohydrates. Hence, α-glucosidase inhibitors can retard the liberation of d-glucose from dietary complex carbohydrates and delay glucose absorption, resulting in reduced postprandial plasma glucose levels and suppression of postprandial hyperglycemia. In recent years, many efforts have been made to identify effective α-glucosidase inhibitors from natural sources in order to develop a physiologic functional food or lead compounds for use against diabetes. Many α-glucosidase inhibitors that are phytoconstituents, such as flavonoids, alkaloids, terpenoids,anthocyanins, glycosides, phenolic compounds, and so on, have been isolated from plants. In the present review, we focus on the constituents isolated from different plants having α-glucosidase inhibitory potency along with IC50 values.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 June 2018
                2018
                : 13
                : 6
                : e0197815
                Affiliations
                [1 ] Biotechnology Institute, Ankara University, Ankara, Turkey
                [2 ] Department of Physical and Analytical Chemistry, University of Jaén, Campus Las Lagunillas S/N, Jaén, Spain
                [3 ] Deparment of Biology, Science Faculty, Selcuk University, Campus, Konya, Turkey
                [4 ] Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, Chieti-Italy
                Institute of Medical Research and Medicinal Plant Studies, CAMEROON
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-6548-7823
                Article
                PONE-D-17-43414
                10.1371/journal.pone.0197815
                5986121
                29864137
                bff2acd3-b32b-43b1-a6e2-c96f2734367b
                © 2018 Bender et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 December 2017
                : 27 March 2018
                Page count
                Figures: 6, Tables: 4, Pages: 21
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Phenols
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzyme Inhibitors
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Sugar Acids
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Sugar Acids
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Carbohydrates
                Monosaccharides
                Sugar Acids
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Physical Sciences
                Chemistry
                Phytochemistry
                Phytochemicals
                Biology and Life Sciences
                Biochemistry
                Plant Biochemistry
                Phytochemicals
                Biology and Life Sciences
                Plant Science
                Plant Biochemistry
                Phytochemicals
                Research and Analysis Methods
                Bioassays and Physiological Analysis
                Cell Analysis
                Cell Viability Testing
                Cell Wound Assay
                Custom metadata
                All relevant data are with the paper. There are no ethical or legal restrictions on sharing data sets.

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