Purpose of the Study: COVID-19 is caused by the SARS-CoV-2 virus that had a global pandemic spread in the last two years. Symptoms of the disease include respiratory distress and, in severe cases may consequently lead...Purpose of the Study: COVID-19 is caused by the SARS-CoV-2 virus that had a global pandemic spread in the last two years. Symptoms of the disease include respiratory distress and, in severe cases may consequently lead to death. Blocking the viral proteins can aid in treating this disease and alleviating its symptoms. Two target proteins of the coronavirus that are hot spots in drug discovery are the papain-like protease PL-pro and the main protease M-pro. PL-pro is an enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread. M-pro is the major protease of SARS-CoV-2, which is a keystone in viral replication and transcription. Methods: In this study, we shed the light on the route of targeting viral proteins for disease alleviation, by targeting the two aforementioned enzymes, PL-pro and M-pro using in silico studies. Docking experiments, using AutoDock algorithms, were performed to predict the inhibitory effect of recently produced synthetic derivatives of curcumin on the viral proteins. Results: Most of the curcumin derivatives have shown variable levels of inhibition, e.g., S1 - S6, mainly on the papain-like protease, and to a lesser extent on the main protease. Conclusion: The results indicated that curcumin derivatives can be potent anti-viral drug of SARS-CoV-2, namely targeting the papain-like protease.展开更多
The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride(C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effect...The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride(C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effects of this compound on Hsp90 ATPase activity. Fluorescence spectroscopy was used to examine the affinity between varying concentrations of C0818 and Hsp90, N-Hsp90, MHsp90 and C-Hsp90. Fluorescence intensities were recorded in the range of 290–510 nm at 293, 303 and 310 K, respectively. A colorimetric assay for inorganic phosphate(based on the formation of a phosphomolybdate complex and the subsequent reaction with malachite green) were used to examine the inhibitory effects of C0818 on Hsp90 ATPase activity. The equilibrium dissociation constant K_D value of C0818 was found to be 23.41270.943 μmol/L. The interaction between C0818 and Hsp90 was driven mainly by electrostatic interactions. C0818 showed the strongest affinity with C-Hsp90. These results conclusively demonstrate the inhibitory activity of C0818 on the activity of Hsp90 ATPase.展开更多
AIM： The compound B19 （C21H22O5） is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potentialantitumor effects. This present study was performed to identify the anti-angiogenic activity of ...AIM： The compound B19 （C21H22O5） is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potentialantitumor effects. This present study was performed to identify the anti-angiogenic activity of this compound. METHODS AND RESULTS： B19 inhibited migration and tube formation of human umbilical vein endothelial cells, and arrested microvessel outgrowth from rat aortic rings.ln addition, B19 suppressed the neovascularization of chicken chorioallantoic membrane. Mechanistic studies revealed that B19 suppressed the downstream protein kinase activation of vascular endothelial growth factor （VEGF） by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, with or without stimulating vascular endothelial growth factor （VEGF）. CONCLUSIONS： B 19 exerted anti-angiogenic activity in vitro and ex vivo, which suggests that it merits further investigation as a promising anticancer angiogenesis compound.展开更多
The three-dimensional quantitative structure-activity relationships(3D-QSAR)for 37 curcumin derivatives were constructed by CoMFA and CoMSIA methods,respectively.The results showed that the cross validated coefficient...The three-dimensional quantitative structure-activity relationships(3D-QSAR)for 37 curcumin derivatives were constructed by CoMFA and CoMSIA methods,respectively.The results showed that the cross validated coefficient(q^2)and non-cross-validated coefficient(R^2)were 0.711,0.962 in CoMFA model and 0.774,0.856 in CoMSIA model,respectively,which suggests that two models are robust and have good exterior predictive capabilities.Based on these two models and the binding mode with tubulin,nine novel curcuminoids inhibitors which could exhibit much higher anticancer potency and efficiently occupy the colchicine binding site of tubulin,were designed.We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent curcumin derivatives with stronger anticancer activities.展开更多
文摘Purpose of the Study: COVID-19 is caused by the SARS-CoV-2 virus that had a global pandemic spread in the last two years. Symptoms of the disease include respiratory distress and, in severe cases may consequently lead to death. Blocking the viral proteins can aid in treating this disease and alleviating its symptoms. Two target proteins of the coronavirus that are hot spots in drug discovery are the papain-like protease PL-pro and the main protease M-pro. PL-pro is an enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread. M-pro is the major protease of SARS-CoV-2, which is a keystone in viral replication and transcription. Methods: In this study, we shed the light on the route of targeting viral proteins for disease alleviation, by targeting the two aforementioned enzymes, PL-pro and M-pro using in silico studies. Docking experiments, using AutoDock algorithms, were performed to predict the inhibitory effect of recently produced synthetic derivatives of curcumin on the viral proteins. Results: Most of the curcumin derivatives have shown variable levels of inhibition, e.g., S1 - S6, mainly on the papain-like protease, and to a lesser extent on the main protease. Conclusion: The results indicated that curcumin derivatives can be potent anti-viral drug of SARS-CoV-2, namely targeting the papain-like protease.
基金the National Science and Technology Foundation of China for Key Projects of“Major New Drugs Innovation and Development”(2012ZX09103-101028)Fujian Provincial Health and Family Planning Commission of China(2015-1-72)the Projects of Industry-Academy Cooperation for Science and Technology of Fujian Province,Chian(2016Y4005)for this project
文摘The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride(C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effects of this compound on Hsp90 ATPase activity. Fluorescence spectroscopy was used to examine the affinity between varying concentrations of C0818 and Hsp90, N-Hsp90, MHsp90 and C-Hsp90. Fluorescence intensities were recorded in the range of 290–510 nm at 293, 303 and 310 K, respectively. A colorimetric assay for inorganic phosphate(based on the formation of a phosphomolybdate complex and the subsequent reaction with malachite green) were used to examine the inhibitory effects of C0818 on Hsp90 ATPase activity. The equilibrium dissociation constant K_D value of C0818 was found to be 23.41270.943 μmol/L. The interaction between C0818 and Hsp90 was driven mainly by electrostatic interactions. C0818 showed the strongest affinity with C-Hsp90. These results conclusively demonstrate the inhibitory activity of C0818 on the activity of Hsp90 ATPase.
基金supported by the National Natural Science Foundation(Nos.81102853,81071841)
文摘AIM： The compound B19 （C21H22O5） is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potentialantitumor effects. This present study was performed to identify the anti-angiogenic activity of this compound. METHODS AND RESULTS： B19 inhibited migration and tube formation of human umbilical vein endothelial cells, and arrested microvessel outgrowth from rat aortic rings.ln addition, B19 suppressed the neovascularization of chicken chorioallantoic membrane. Mechanistic studies revealed that B19 suppressed the downstream protein kinase activation of vascular endothelial growth factor （VEGF） by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, with or without stimulating vascular endothelial growth factor （VEGF）. CONCLUSIONS： B 19 exerted anti-angiogenic activity in vitro and ex vivo, which suggests that it merits further investigation as a promising anticancer angiogenesis compound.
基金Supported by National Natural Science Foundation of China (2170203421861007)+2 种基金the Research Foundation of Education Bureau of Guangxi Province (200103YB076)Natural Science Foundation of Guangxi Province (2017GXNSFBA198089)“BAGUI Scholar” Program of Guangxi Province of China。
文摘The three-dimensional quantitative structure-activity relationships(3D-QSAR)for 37 curcumin derivatives were constructed by CoMFA and CoMSIA methods,respectively.The results showed that the cross validated coefficient(q^2)and non-cross-validated coefficient(R^2)were 0.711,0.962 in CoMFA model and 0.774,0.856 in CoMSIA model,respectively,which suggests that two models are robust and have good exterior predictive capabilities.Based on these two models and the binding mode with tubulin,nine novel curcuminoids inhibitors which could exhibit much higher anticancer potency and efficiently occupy the colchicine binding site of tubulin,were designed.We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent curcumin derivatives with stronger anticancer activities.
