title: Antioxidant properties of select radiation mitigators based on semicarbazone and pyrazole derivatives of curcumin.
abstract: Fifty-eight semicarbazone and pyrazole derivatives of curcumin have been developed as potential mitigation agents to treat acute radiation syndrome (ARS). Pyridyl (D12, D13), furyl (D56), and phenyl (D68) derivatives of curcumin semi-carbazones were found to provide the highest dose modifying factors (DMF) with respect to survival in sub-TBI (bone marrow sparing) exposures in mouse models. To investigate the basis for the mitigating effects of these agents on ARS, we examined their oxidation potentials and radical scavenging properties in comparison to other semicarbazone and pyrazole curcumin derivatives with less effective DMFs. Comparisons between D12, D13, D56, and D68 and other semicarbazone and pyrazole derivatives of curcumin did not show a sufficient difference in reducing properties and hydrogen atom donating properties for these properties to be the basis of the dose modifying activities of these compounds. Therefore, their DMFs likely reflect structure-activity relationship(s),wherein interaction with key receptors or alteration of enzyme expression result in modifications of cellular or tissue responses to radiation, rather than on the derivatives' ability to modify radiation-induced flux of free radicals through direct interaction with these radicals.
authors: Department of Radiation Oncology, University of Florida, 2033 Mowry Road, 103633, Gainesville, FL 32610, USA. sgswarts@ufl.edu
authors: Steven G
authors: SG
authors: Swarts
authors: Mei
authors: M
authors: Zhang
authors: Liangjie
authors: L
authors: Yin
authors: Chaomei
authors: C
authors: Liu
authors: Yeping
authors: Y
authors: Tian
authors: Yongbing
authors: Y
authors: Cao
authors: Michael
authors: M
authors: Swarts
authors: David J
authors: DJ
authors: Olek
authors: Lisa
authors: L
authors: Schwartz
authors: Louie
authors: L
authors: Zhang
authors: Shanmin
authors: S
authors: Yang
authors: Steven B
authors: SB
authors: Zhang
authors: Kunzhong
authors: K
authors: Zhang
authors: Shaoqing
authors: S
authors: Ju
authors: Sadasivan
authors: S
authors: Vidyasagar
authors: Lurong
authors: L
authors: Zhang
authors: Paul
authors: P
authors: Okunieff
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008982:Molybdenum / Q000378:metabolism; D010084:Oxidation-Reduction; D010756:Phosphoric Acids / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012664:Semicarbazones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014916:Whole-Body Irradiation
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D010756:Phosphoric Acids; D011720:Pyrazoles; D011837:Radiation-Protective Agents; D012664:Semicarbazones; C031280:pyrazole; D008982:Molybdenum; D003474:Curcumin; C003125:phosphomolybdic acid