A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5￣8 days after acute myocardial infarction. The electrophysiologic e...A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5￣8 days after acute myocardial infarction. The electrophysiologic effects of sophoridine (Sop) and procainamide (PA) were observed in this canine model. With routine methods of PES, ventricular tachycardia (VT) and ventricular fibrilation (VF) could be reproducibly initiated in this model. Both drugs distinctly lengthened the QTc interval ( P <0.01) and the effective refractory period (ERP) in normal and ischemic ventricular myocardium ( P <0.01), decreased the dispersion of ERP in ischemic myocardium and the dispersion of ERP in left ventricle (P <0.05), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably ( P <0.01). Both drugs effectively prevented the PES-induced VT or VF and ischemia-induced VF ( P <0.05). The results indicated that this canine model is a good and reliable one, sophoridine and procainamide may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardial ischemic damage.展开更多
Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The cry...Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The crystal belongs to the orthorhombic system,space group P212121 with a = 8.321（2）,b = 15.650（3）,c = 24.352（5） ,V = 3171.1（11） 3,Z = 8,Dc = 1.258 g/cm3,λ（CuKα） = 1.54178,F（000） = 1440,the final R = 0.0351 and wR = 0.0970.The crystal structure shows Sophoridine N-oxide crystallizes with two host molecules of similar conformation and four water solvent molecules in the asymmetric unit.In the crystal structure,intermolecular O-H…O hydrogen bonds link the constituent molecules into a 2D layer structure,which further extends to a 3D supramolecular architecture via Van der Waals interactions and intermolecular O-H…O hydrogen bonds.展开更多
Sophoridine N -oxide (A) was isolated from the seeds of Inner MongolianSophora alopecuroides L. Its structure was characteraized. Deoxygenation of A gave sophoridine whereas N-oxidation of sophoridine gave two N-oxide...Sophoridine N -oxide (A) was isolated from the seeds of Inner MongolianSophora alopecuroides L. Its structure was characteraized. Deoxygenation of A gave sophoridine whereas N-oxidation of sophoridine gave two N-oxides, The stereochernical featuresof the two isomers were given by analysis of its 1H-and 13C-NMR spetra.展开更多
Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from soph...Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.展开更多
Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity...Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity relationship analysis indicated:(i) 12 N-dichlorobenzyl motif was beneficial for the activity;(ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC_(50) value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.展开更多
文摘A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5￣8 days after acute myocardial infarction. The electrophysiologic effects of sophoridine (Sop) and procainamide (PA) were observed in this canine model. With routine methods of PES, ventricular tachycardia (VT) and ventricular fibrilation (VF) could be reproducibly initiated in this model. Both drugs distinctly lengthened the QTc interval ( P <0.01) and the effective refractory period (ERP) in normal and ischemic ventricular myocardium ( P <0.01), decreased the dispersion of ERP in ischemic myocardium and the dispersion of ERP in left ventricle (P <0.05), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably ( P <0.01). Both drugs effectively prevented the PES-induced VT or VF and ischemia-induced VF ( P <0.05). The results indicated that this canine model is a good and reliable one, sophoridine and procainamide may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardial ischemic damage.
基金supported by Tianjin key Technology R&D Program (No. 07ZCKFSH00200)
文摘Sophoridine N-oxide was synthesized and characterized by 1H-NMR,EI-MS,IR and elemental analysis,together with X-ray single-crystal diffraction analysis,and its crystal structure was reported for the first time.The crystal belongs to the orthorhombic system,space group P212121 with a = 8.321（2）,b = 15.650（3）,c = 24.352（5） ,V = 3171.1（11） 3,Z = 8,Dc = 1.258 g/cm3,λ（CuKα） = 1.54178,F（000） = 1440,the final R = 0.0351 and wR = 0.0970.The crystal structure shows Sophoridine N-oxide crystallizes with two host molecules of similar conformation and four water solvent molecules in the asymmetric unit.In the crystal structure,intermolecular O-H…O hydrogen bonds link the constituent molecules into a 2D layer structure,which further extends to a 3D supramolecular architecture via Van der Waals interactions and intermolecular O-H…O hydrogen bonds.
文摘Sophoridine N -oxide (A) was isolated from the seeds of Inner MongolianSophora alopecuroides L. Its structure was characteraized. Deoxygenation of A gave sophoridine whereas N-oxidation of sophoridine gave two N-oxides, The stereochernical featuresof the two isomers were given by analysis of its 1H-and 13C-NMR spetra.
基金supported by the National Natural Science Foundation of China(No.81473248)Tianjin Medical University General Hospital Funding(ZYYFY2015030)
文摘Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
基金supported by the National Natural Science Foundation of China (Nos. 81673307 and 81321004)CAMS Innovation Fund for Medical Sciences (2016–I2M–3–009)
文摘Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity relationship analysis indicated:(i) 12 N-dichlorobenzyl motif was beneficial for the activity;(ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC_(50) value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.
