In this study,a method was developed to form C(sp^(3))-C(sp^(2))bonds via copper catalyst-promoted cross coupling of 2-methylquinoline and in-situ-activated 3-haloisoquinoline under mild conditions.The multi-component...In this study,a method was developed to form C(sp^(3))-C(sp^(2))bonds via copper catalyst-promoted cross coupling of 2-methylquinoline and in-situ-activated 3-haloisoquinoline under mild conditions.The multi-component tandem reaction was used to construct new C-N,C=O and C-C bonds in one pot via sequential functionalization of the N1,C3 and C1 positions of 3-haloisoquinoline.This method can be used to efficiently access 1,2-disubstituted isoquinolinones by the three-component reaction of 3-halogen isoquinoline,alkyl halide,and 2-methylquinoline.展开更多
The first total synthesis of isoquinolinone alkaloid marinamide 1 and its methyl ester 2 was described. The key steps involved a regioselective Frieclel-Crafts reaction of 1-benzyl-1H-pyrrole to form the intermediate 8.
Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoqu...Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.展开更多
基金Foundation of the National Natural Science Foundation of China(No.22101212)“Climbing Program”(No.pdjh2021a0505)Special Funds+2 种基金Science Foundation for Young Teachers of Wuyi University(No.2019td06)Guangdong Basic and Applied Basic Research Foundation(Nos.2019A1515110866,2019A1515110522)College Students Innovation and Entrepreneurship Training Program of Wuyi University(Nos.202111349020,202111349308S)for financial support。
文摘In this study,a method was developed to form C(sp^(3))-C(sp^(2))bonds via copper catalyst-promoted cross coupling of 2-methylquinoline and in-situ-activated 3-haloisoquinoline under mild conditions.The multi-component tandem reaction was used to construct new C-N,C=O and C-C bonds in one pot via sequential functionalization of the N1,C3 and C1 positions of 3-haloisoquinoline.This method can be used to efficiently access 1,2-disubstituted isoquinolinones by the three-component reaction of 3-halogen isoquinoline,alkyl halide,and 2-methylquinoline.
基金the National Basic Research of China(No. 2011CB933503) for financial support
文摘The first total synthesis of isoquinolinone alkaloid marinamide 1 and its methyl ester 2 was described. The key steps involved a regioselective Frieclel-Crafts reaction of 1-benzyl-1H-pyrrole to form the intermediate 8.
基金This study was supported by grants from the Natural Science Foundation of Shandong Province, China （No.ZR2010HM069） and the Technology Development Projects of Taian City （No. 20093077）.
文摘Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.
