title: Mechanochemical Synthesis and Antioxidant Activity of Curcumin-Templated Azoles.
abstract: A solvent-free, mechanochemical method for the synthesis of curcumin (1) derived 3,5-bis(styryl)pyrazoles and 3,5-bis(styryl)isoxazole (2a-g) at room temperature, with very short reaction time, is reported. Such earlier structural modifications of curcumin, at its β-diketone unit by transforming it into an isosteric pyrazole or isoxazole unit, required prolonged heating. The evaluation of the antioxidant activity of these compounds, based on DPPH, FRAP, and β-carotene bleaching assays, showed that several of these azoles are better antioxidants than curcumin, with the isoxazole derivative 2g being overall the best. Typically, the inhibition of 2,2-diphenyl-1-picrylhydrazyl (10(-2) mmol), expressed as EC50 values, by curcumin (1), 3,5-bis(4-hydroxy-3-methoxystyryl)pyrazole (2a), and 3,5-bis(4-hydroxy-3-methoxystyryl)isoxazole (2g) are 40 ± 0.06, 14 ± 0.18, and 8 ± 0.11 μmol, respectively. Moreover, the reported method is useful in accessing 3,5-bis(4-hydroxy-3-methoxystyryl)-1-phenylpyrazole (2b), which is important in studies related to neuroprotection and Alzheimer's disease, and 2a and 2g, which are inhibitors of protein kinases involved in neuronal excitotoxicity.
authors.affiliation: Department of Chemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala, India.
authors.forename: Daisy R
authors.initials: DR
authors.lastname: Sherin
authors.affiliation: Department of Chemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala, India.
authors.forename: Kallikat N
authors.initials: KN
authors.lastname: Rajasekharan
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D036681:Fluorescence Recovery After Photobleaching; D015394:Molecular Structure; D010851:Picrates / Q000737:chemistry; D013329:Structure-Activity Relationship; D019207:beta Carotene / Q000737:chemistry
chemical_list: D000975:Antioxidants; D001393:Azoles; D001713:Biphenyl Compounds; D010851:Picrates; D019207:beta Carotene; C004931:1,1-diphenyl-2-picrylhydrazyl; D003474:Curcumin
keywords: 3,5-Bis(styryl)pyrazole/isoxazole; Antioxidant; Curcumin; Mechanochemical