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001-es BibID:BIBFORM082556
035-os BibID:(WoS)000503330800047 (Scopus)85076051798
Első szerző:Johnston, Hannah M.
Cím:Enhancement of the Antioxidant Activity and Neurotherapeutic Features through Pyridol Addition to Tetraazamacrocyclic Molecules / Hannah M. Johnston, Kristof Pota, Madalyn M. Barnett, Olivia Kinsinger, Paige Braden, Timothy M. Schwartz, Emily Hoffer, Nishanth Sadagopan, Nam Nguyen, Yu Yu, Paulina Gonzalez, Gyula Tircsó, Hongli Wu, Giridhar Akkaraju, Michael J. Chumley, Kayla N. Green
Dátum:2019
ISSN:0020-1669 1520-510X
Megjegyzések:Alzheimer's and other neurodegenerative diseases are chronic conditions affecting millions of individuals worldwide. Oxidative stress is a consistent component described in the development of many neurodegenerative diseases. Therefore, innovative strategies to develop drug candidates that overcome oxidative stress in the brain are needed. To target these challenges, a new, water-soluble 12-membered tetraaza macrocyclic pyridinophane L4 was designed and produced using a building-block approach. Potentiometric data show that the neutral species of L4 provides interesting zwitterionic behavior at physiological pH, akin to amino acids, and a nearly ideal isoelectric point of 7.3. The copper(II) complex of L4 was evaluated by X-ray diffraction and cyclic voltammetry to show the potential modes of antioxidant activity derived, which was also demonstrated by 2,2-diphenyl-1-picrylhydrazyl and coumarin carboxylic acid antioxidant assays. L4 was shown to have dramatically enhanced antioxidant activity and increased biological compatibility compared to parent molecules reported previously. L4 attenuated hydrogen peroxide (H2O2)-induced cell viability loss more efficiently than precursor molecules in the mouse hippocampal HT-22 cell model. L4 also showed potent (fM) level protection against H2O2 cell death in a BV2 microglial cell culture. Western blot studies indicated that L4 enhanced the cellular antioxidant defense capacity via Nrf2 signaling activation as well. Moreover, a low-cost analysis and high metabolic stability in phase I and II models were observed. These encouraging results show how the rational design of lead compounds is a suitable strategy for the development of treatments for neurodegenerative diseases where oxidative stress plays a substantial role.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Inorganic Chemistry. - 58 : 24 (2019), p. 16771-16784. -
További szerzők:Póta Kristóf Barnett, Madalyn M. Kinsinger, Olivia Braden, Paige Schwartz, Timothy M. Hoffer, Emily Sadagopan, Nishanth Nguyen, Nam Yu, Yu Gonzalez, Paulina Tircsó Gyula (1977-) (vegyész, kémia tanár) Wu, Hongli Akkaraju, Giridhar Chumley, Michael J. Green, Kayla N.
Pályázati támogatás:NKFIH K-120224
egyéb
ÚNKP-18-4
egyéb
GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
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