title: Probing antioxidant activity of 2'-hydroxychalcones: crystal and molecular structures, in vitro antiproliferative studies and in vivo effects on glucose regulation.
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.
authors.affiliation: Vassar College, Department of Chemistry, Box 484, Poughkeepsie, NY 12604-0484, USA. Rossi@vassar.edu
authors.forename: Miriam
authors.initials: M
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Caruso
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Crespi
authors.forename: Jens Z
authors.initials: JZ
authors.lastname: Pedersen
authors.forename: Gail
authors.initials: G
authors.lastname: Nakano
authors.forename: Michelle
authors.initials: M
authors.lastname: Duong
authors.forename: Celia
authors.initials: C
authors.lastname: McKee
authors.forename: Sharon
authors.initials: S
authors.lastname: Lee
authors.forename: Manasi
authors.initials: M
authors.lastname: Jiwrajka
authors.forename: Charles
authors.initials: C
authors.lastname: Caldwell
authors.forename: Francis
authors.initials: F
authors.lastname: Baffour
authors.forename: Dylan Alex
authors.initials: DA
authors.lastname: Karlin
authors.forename: Genevieve
authors.initials: G
authors.lastname: Lidoff
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.forename: Valentina
authors.initials: V
authors.lastname: Balducci
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Miler
authors.forename: Sandra
authors.initials: S
authors.lastname: Incerpi
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010851:Picrates / Q000037:antagonists & inhibitors; D051381:Rats; D011924:Rats, Zucker
chemical_list: D019440:Anti-Obesity Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D001786:Blood Glucose; D047188:Chalcones; D007004:Hypoglycemic Agents; D007328:Insulin; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: 2,2′,5′-trihydroxychalcone; 2′,3′,4′-trihydroxychalcone; 2′,4,4′-trihydroxychalcone; 2′,4-dihydroxychalcone; CHALCO1; CHALCO2; CHALCO3; CHALCO4; Chalcone antioxidant; Free radical scavenger; Glucose regulation; L-6 myoblasts; THP-1 monocytes