Improved synthesis and structure identification of L-histidine norcantharimide , a potent PP2A inhibitor was reported. Condensation between norcantharidin and L-histidine in 95% EtOH at reflux temperature affords L-hi...Improved synthesis and structure identification of L-histidine norcantharimide , a potent PP2A inhibitor was reported. Condensation between norcantharidin and L-histidine in 95% EtOH at reflux temperature affords L-histidine norcantharimide in 97.0f% yield which is much higher compared with literature, and more importantly, the configuration is retained. The chemical structure of the compound was re-elucidated through IR, FAB-MS, ^1H NMR, ^13C NMR and 2D NMR （^1H, ^13C-COSY and HMBC）, the fundamental physical data, including optical data being also firstly reported. Preliminary cytotoxicity evaluation showed that the target compound was probably more potent than norcantharidin against a panel of human cancer cell lines. Design and synthesis of amino acid （nor） cantharirnides would provide a convenient and rational structure modification of （nor） cantharidin and open new avenues to explore new promising candidates.展开更多
A novel nickel（Ⅱ） complex with L-histidine has been synthesized and solved by single-crystal X-ray diffraction analysis at physiological pH. The title complex （C7H16NiN4O6S, Mr = 343.01） crystallizes in monoclini...A novel nickel（Ⅱ） complex with L-histidine has been synthesized and solved by single-crystal X-ray diffraction analysis at physiological pH. The title complex （C7H16NiN4O6S, Mr = 343.01） crystallizes in monoclinic, space group P21 with a = 7.2194（7）, b = 7.5968（7）, c = 12.2797（11） A, β = 93.3110（10）°, V = 672.35（11） A^3, Z = 2, Dc= 1.694 g/cm^3, F（000） = 356, μ（MoKα） = 1.626 mm^-1, T = 293（2） K, the final R = 0.0184 and wR = 0.0426 for 2207 observed reflections with 1 〉 2σ（I）. The complex provides insights into a possible structural arrangement between nickel （Ⅱ） and L-histidine which may be physiologically important and abundantly present in biological systems.展开更多
The ternary complexes containing Cu(II),L-His and nucleotide (5'-GMP and 5'-IMP)were synthesized and characterized.IR and ~1H NMR spectra show that Cu(II)binds to carboxylate oxygen and imidazole nitrogen of L...The ternary complexes containing Cu(II),L-His and nucleotide (5'-GMP and 5'-IMP)were synthesized and characterized.IR and ~1H NMR spectra show that Cu(II)binds to carboxylate oxygen and imidazole nitrogen of L-His and purine N_7 of 5'-GMP and 5'-IMP.The interaction of Cu(II)with Po_3^(2-)of 5'-GMP is present,but that for 5'-IMP is not present.展开更多
Background and aims:Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.The mechanisms driving the transition from hepatitis to cirrhosis,and eventually,to HCC are unclear.This s...Background and aims:Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.The mechanisms driving the transition from hepatitis to cirrhosis,and eventually,to HCC are unclear.This study aimed to clarify the metabolic changes that underly the progression of HCC and identify potential prognostic and therapeutic biomarkers.Methods:This prospective study collected serum samples from patients with chronic hepatitis,cirrhosis,or HCC,hospitalized at the Fifth Medical Center of the PLA General Hospital,from December 2022 to December 2023.The samples were analyzed using non-targeted,ultra-high-performance liquid chromatography and mass spectrometry.Partial least squares-discriminant analysis modeling and t-tests were used to identify key differentially expressed metabolites associated with the progression from hepatitis to cirrhosis to HCC.Pathway enrichment analysis was conducted to determine the key metabolic pathways involved,while machine learning models were applied to identify the metabolite signatures.Results:We identified 153 differentially expressed metabolites in the progression from hepatitis to cirrhosis to HCC,many of which were involved in ammonia cycling or the metabolism of methylhistidine,alanine,arginine,proline,or betaine.We also identified L-histidine and adenosine as the metabolites that demonstrated significant sensitivity and specificity for distinguishing among the hepatitis,cirrhosis,and HCC stages.Conclusions:Our study comprehensively characterized the metabolic profiles of the different stages of the hepatitis-cirrhosis-HCC transition.We showed that serum metabolite detection is a viable diagnostic tool for identifying and monitoring high-risk individuals,which could potentially be used to halt the development of HCC.展开更多
基金Science and Technology Program of Guangdong Province(Grant No.2006B35604002)Guangzhou City(Grant No.2007JI-C0261).
文摘Improved synthesis and structure identification of L-histidine norcantharimide , a potent PP2A inhibitor was reported. Condensation between norcantharidin and L-histidine in 95% EtOH at reflux temperature affords L-histidine norcantharimide in 97.0f% yield which is much higher compared with literature, and more importantly, the configuration is retained. The chemical structure of the compound was re-elucidated through IR, FAB-MS, ^1H NMR, ^13C NMR and 2D NMR （^1H, ^13C-COSY and HMBC）, the fundamental physical data, including optical data being also firstly reported. Preliminary cytotoxicity evaluation showed that the target compound was probably more potent than norcantharidin against a panel of human cancer cell lines. Design and synthesis of amino acid （nor） cantharirnides would provide a convenient and rational structure modification of （nor） cantharidin and open new avenues to explore new promising candidates.
基金This work was supported by the National Natural Science Foundation of China (No. 50572040)
文摘A novel nickel（Ⅱ） complex with L-histidine has been synthesized and solved by single-crystal X-ray diffraction analysis at physiological pH. The title complex （C7H16NiN4O6S, Mr = 343.01） crystallizes in monoclinic, space group P21 with a = 7.2194（7）, b = 7.5968（7）, c = 12.2797（11） A, β = 93.3110（10）°, V = 672.35（11） A^3, Z = 2, Dc= 1.694 g/cm^3, F（000） = 356, μ（MoKα） = 1.626 mm^-1, T = 293（2） K, the final R = 0.0184 and wR = 0.0426 for 2207 observed reflections with 1 〉 2σ（I）. The complex provides insights into a possible structural arrangement between nickel （Ⅱ） and L-histidine which may be physiologically important and abundantly present in biological systems.
文摘The ternary complexes containing Cu(II),L-His and nucleotide (5'-GMP and 5'-IMP)were synthesized and characterized.IR and ~1H NMR spectra show that Cu(II)binds to carboxylate oxygen and imidazole nitrogen of L-His and purine N_7 of 5'-GMP and 5'-IMP.The interaction of Cu(II)with Po_3^(2-)of 5'-GMP is present,but that for 5'-IMP is not present.
基金funded by the National Natural Science Foundation of China(grant number 81673806)the Medical Education Association Foundation of China(grant number 2020KTY001).
文摘Background and aims:Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.The mechanisms driving the transition from hepatitis to cirrhosis,and eventually,to HCC are unclear.This study aimed to clarify the metabolic changes that underly the progression of HCC and identify potential prognostic and therapeutic biomarkers.Methods:This prospective study collected serum samples from patients with chronic hepatitis,cirrhosis,or HCC,hospitalized at the Fifth Medical Center of the PLA General Hospital,from December 2022 to December 2023.The samples were analyzed using non-targeted,ultra-high-performance liquid chromatography and mass spectrometry.Partial least squares-discriminant analysis modeling and t-tests were used to identify key differentially expressed metabolites associated with the progression from hepatitis to cirrhosis to HCC.Pathway enrichment analysis was conducted to determine the key metabolic pathways involved,while machine learning models were applied to identify the metabolite signatures.Results:We identified 153 differentially expressed metabolites in the progression from hepatitis to cirrhosis to HCC,many of which were involved in ammonia cycling or the metabolism of methylhistidine,alanine,arginine,proline,or betaine.We also identified L-histidine and adenosine as the metabolites that demonstrated significant sensitivity and specificity for distinguishing among the hepatitis,cirrhosis,and HCC stages.Conclusions:Our study comprehensively characterized the metabolic profiles of the different stages of the hepatitis-cirrhosis-HCC transition.We showed that serum metabolite detection is a viable diagnostic tool for identifying and monitoring high-risk individuals,which could potentially be used to halt the development of HCC.
