ABSTRACT
Excessive levels of reactive oxygen species (ROS) and impaired Ca2+ homeostasis play central roles in the development of multiple cardiac pathologies, including cell death during ischemia-reperfusion (I/R) injury. In several organs, treatment with 2-aminoethoxydiphenyl borate (2-APB) was shown to have protective effects, generally believed to be due to Ca2+ channel inhibition. However, the mechanism of 2-APB-induced cardioprotection has not been fully investigated. Herein we investigated the protective effects of 2-APB treatment against cardiac pathogenesis and deciphered the underlying mechanisms. In neonatal rat cardiomyocytes, treatment with 2-APB was shown to prevent hydrogen peroxide (H2O2) -induced cell death by inhibiting the increase in intracellular Ca2+ levels. However, no 2-APB-sensitive channel blocker inhibited H2O2-induced cell death and a direct reaction between 2-APB and H2O2 was detected by 1H-NMR, suggesting that 2-APB chemically scavenges extracellular ROS and provides cytoprotection. In a mouse I/R model, treatment with 2-APB led to a considerable reduction in the infarct size after I/R, which was accompanied by the reduction in ROS levels and neutrophil infiltration, indicating that the anti-oxidative properties of 2-APB plays an important role in the prevention of I/R injury in vivo as well. Taken together, present results indicate that 2-APB treatment induces cardioprotection and prevents ROS-induced cardiomyocyte death, at least partially, by the direct scavenging of extracellular ROS. Therefore, administration of 2-APB may represent a promising therapeutic strategy for the treatment of ROS-related cardiac pathology including I/R injury.
Subject(s)
Antioxidants/pharmacology , Boron Compounds/pharmacology , Reperfusion Injury/prevention & control , Animals , Mice , Reactive Oxygen Species/metabolismABSTRACT
For an Ir-doped TiO2 (Ir:TiO2) photocatalyst, we examined the most dominant electron-transfer path for the visible-light-driven photocatalytic performance. The Ir:TiO2 photocatalyst showed a much higher photocatalytic activity under visible-light irradiation than nondoped TiO2 after grafting with the cocatalyst of Fe3+. For the Ir:TiO2 photocatalyst, the two-step photoexcitation of an electron from the valence band to the conduction band through the Ir doping level occurred upon visible-light irradiation, as observed by electron spin resonance spectroscopy. The two-step photoexcitation through the doping level was found to be a more stable process with a lower recombination rate of hole-electron pairs than the two-step photoexcitation process through an oxygen vacancy. Once electrons are photoexcited to the conduction band by the two-step excitation, the electrons can easily transfer to the surface because the conduction band is a continuous electron path, whereas the electrons photoexcited at only the doping level could not easily transfer to the surface because of the discontinuity of this path. The observed two-step photoexcitation from the valence band to the conduction band through the doping level significantly contributes to the enhancement of the photocatalytic performance.
ABSTRACT
A new synthetic route to clavilactone B, a naturally occurring inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is disclosed. The route features a sequential samarium-mediated radical cyclization-fragmentation of an indanone derivative, which provides rapid access to a 10-membered carbocyclic motif fused to an aromatic ring.
Subject(s)
ErbB Receptors/antagonists & inhibitors , Lactones/chemical synthesis , Crystallography, X-Ray , Cyclization , Iodides/chemistry , Lactones/chemistry , Molecular Conformation , Molecular Structure , Samarium/chemistryABSTRACT
A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Light , Naphthols/chemical synthesis , Phenols/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cyclization , Humans , Molecular Structure , Naphthols/chemistry , Naphthols/pharmacology , StereoisomerismABSTRACT
The first synthesis of decahydrofluorene core 4 of pyrrocidines was accomplished. The cis,trans-fused tricyclic ring system was stereoselectively constructed via Diels-Alder reaction using two Danishefsky dienes.
