Probing antioxidant activity of 2′-hydroxychalcones: Crystal and molecular structures, in vitro antiproliferative studies and in vivo effects on glucose regulation |
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Authors: | Miriam Rossi Francesco Caruso Erica J Crespi Jens Z Pedersen Gail Nakano Michelle Duong Celia Mckee Sharon Lee Manasi Jiwrajka Charles Caldwell Francis Baffour Dylan Alex Karlin Genevieve Lidoff Stefano Leone Valentina Balducci Jaroslav Miler Sandra Incerpi |
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Institution: | 1. Vassar College, Department of Chemistry, Box 484, Poughkeepsie, NY 12604-0484, USA;2. Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), c/o University of Rome “La Sapienza”, Istituto Chimico, Piazzale Aldo Moro 5, 00185 Rome, Italy;3. School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA;4. Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Roma, Italy;5. Bard College, Department of Biology, Annandale-on-Hudson, NY, USA;6. Department of Sciences, University Roma Tre, Viale G. Marconi, 446, 00146 Rome, Italy;g Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University of Prague, Czech Republic |
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Abstract: | In order to better understand the antioxidant behavior of a series of polyphenolic 2′-hydroxychalcones, we describe the results of several chemical and biological studies, in vitro and in vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as H-bonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity. The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV–vis spectroscopic method indicate that a hydroxyl group in position 5′ induces the highest antioxidant activity. Consequently, 2,2′,5′-trihydroxychalcone was selected for further study in vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules. In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2′,5′-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa−/fa−) rats we found that supplementing the diet with a 10 mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period. It is concluded that 2,2′,5′-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases. |
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Keywords: | Chalcone antioxidant Free radical scavenger THP-1 monocytes L-6 myoblasts Glucose regulation |
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