Platinum containing compounds have shown antineoplastic potential, but their clinical applications have been limited by high toxicity. Ruthenium containing complexes have long been known to be well suited for biologic...Platinum containing compounds have shown antineoplastic potential, but their clinical applications have been limited by high toxicity. Ruthenium containing complexes have long been known to be well suited for biological applications, and have long been utilized as replacements to popular platinum based-drugs. Here, we report a novel series of ruthenium(ll) arene compounds bearing thiosemicarba- zone and isonicotinylhydrazone ligands with potent anticancer activity their structure activity relationships and apoptosis was studied. The cytotoxic activity of the new ruthenium(ll) arene compounds has been evaluated in several cell lines (Molt 4/C8, LI 210, CEM, HL60 and BEL7402). Among them, ten complexes were found to be excellent in vitro growth inhibitory activity against various cell lines with IC50 in the sub-micromolar range.展开更多
Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive ...Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.展开更多
A method for the analysis of the relationship between the helical structure and optical activity was proposed by the study of the conformations and X-ray diffraction structures of some cyclic esters prepared by esteri...A method for the analysis of the relationship between the helical structure and optical activity was proposed by the study of the conformations and X-ray diffraction structures of some cyclic esters prepared by esterification of L-(-)-2.3-O-methylidene threitol and L-(+)-2,3-O-isopropplidene threitol with alkanedioyl dichlorides and o-,m-,and p-phthaloyl dichlorides.展开更多
Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in va...Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.展开更多
Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment o...Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.展开更多
Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective ...Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.展开更多
Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.H...Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.Here,we develop a strategy to dilute catalytically active metal interatomic spacing(d_(M-M))with light atoms and discover the unusual adsorption patterns.For example,by elevating the content of boron as interstitial atoms,the atomic spacing of osmium(d_(Os-Os))gradually increases from 2.73 to 2.96?.More importantly,we find that,with the increase in dOs-Os,the hydrogen adsorption-distance relationship is reversed via downshifting d-band states,which breaks the traditional cognition,thereby optimizing the H adsorption and H_2O dissociation on the electrode surface during the catalytic process;this finally leads to a nearly linear increase in hydrogen evolution reaction activity.Namely,the maximum dOs-Os of 2.96?presents the optimal HER activity(8 mV@10 mA cm^(-2))in alkaline media as well as suppressed O adsorption and thus promoted stability.It is believed that this novel atomic-level distance modulation strategy of catalytic sites and the reversed hydrogen adsorption-distance relationship can shew new insights for optimal design of highly efficient catalysts.展开更多
To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
A series of trihydrocarbyltin chlorides containing silicon was synthesized. The acaricidal activity was determined and the structure activity relationship was tried to be found out with the hydrophobic parameter.
The isolated secondary metabolites from 39 edible mushrooms are reported,among which 107 compounds were active,61 demonstrated antitubercular activities with IC_(50) range of 0.2-50μg/mL and 46 manifested antimalaria...The isolated secondary metabolites from 39 edible mushrooms are reported,among which 107 compounds were active,61 demonstrated antitubercular activities with IC_(50) range of 0.2-50μg/mL and 46 manifested antimalarial effects with IC_(50) range of 0.061-36μg/mL.While more than 2000 strains of edible mushrooms are identified,this review shows the paucity of research in these rich organisms featuring a vital culinary ingredient worldwide.A thorough search was conducted on basidiomycetes to discuss the chemistry and biology of the isolated compounds,structure activity relationships(SAR)as well as the cytotoxicity profiles of,primarily,the active anti-plasmodial and antitubercular molecules.With a safe cellular profile,lanostane triterpenoids were found to be the only molecules with combined activities against both diseases.SAR correlations reviewed here indicated the significance of 3β-and 7α-hydroxylation in the anti-tuberculosis activity and the terminal unsaturated moiety between C-4 and C-28 in the antimalarial activity in the same terpene skeleton.This review will attract the attention of medicinal chemists,and food scientists to optimize and rationalize the use of mushrooms both as unexploited sources of novel molecules and as nutraceuticals to treat two of the deadliest infectious diseases,malaria,and tuberculosis.展开更多
Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as antioxidant,anti-tumor,anti-microbial and anti-inflammatory activities.It is believed that the mechanisms involved in the...Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as antioxidant,anti-tumor,anti-microbial and anti-inflammatory activities.It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system.Recently,the pharmacological validation on immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity.In this review,we have highlighted several studies on immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models.This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship.Hence,the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial immunomodulatory properties.展开更多
Effects of carboxylic acid collector, benzohydroxamic acid (BHA), sodium hexametaphosphate (SHAP), sodium silicate, and oxalic acid on scheelite flotation were studied through flotation tests, quantum chemical calcula...Effects of carboxylic acid collector, benzohydroxamic acid (BHA), sodium hexametaphosphate (SHAP), sodium silicate, and oxalic acid on scheelite flotation were studied through flotation tests, quantum chemical calculation, and flotation solution computational chemistry. In terms of the calculation results, the relationship between chemical reactions occurring on the scheelite surface and molecular structures of the reagents were analyzed. The results show that BHA and carboxylic acid collectors interact with scheelite in different forms and the recovery of scheelite using sodium oleate as collector declines successively from SHAP, sodium silicate, to oxalic acid. Moreover, it is found that the performance of depressant in scheelite flotation is directly related to the group electronegativity, indicating that the latter is a dominant factor that determines the former. These findings will be helpful to the academic research communities of scheelite flotation.展开更多
Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allo...Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.展开更多
C-glycosylflavonoids are characterized by a bond between the anomeric carbon of a sugar moiety and the C-6 or C-8 position of a flavonoid A ring.These compounds are widespread in nature and have become the subject of ...C-glycosylflavonoids are characterized by a bond between the anomeric carbon of a sugar moiety and the C-6 or C-8 position of a flavonoid A ring.These compounds are widespread in nature and have become the subject of increasing research interest due to their high biological potential.This review focuses on the biological effects of various C-glycosylflavonoids and their structure–activity relationships(SAR)as elucidated over the last 5 years.展开更多
The medicinal part of Aucklandia lappa(Asteraceae) is its dried root,which is one of the commonly used Chinese medicinal materials.Here we reviewed sesquiterpene lactones isolated from A.lappa over the past ten years ...The medicinal part of Aucklandia lappa(Asteraceae) is its dried root,which is one of the commonly used Chinese medicinal materials.Here we reviewed sesquiterpene lactones isolated from A.lappa over the past ten years in the following aspects of pharmacological activities,pharmacokinetics,toxicology,structure-activity relationship.Pharmacological activities consist of anti-cancer,anti-inflammatory activity,anti-immunity activity,anti-oxidant activity,antimicrobial activity,spasmolytic activity and so on.The extractive,showing similar pharmacokinetics parameters,may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition.However,the poor aqueous solubility,non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class.In order to evaluate the potential effect of the extractive applied in clinical trial,the present review outlines information on pharmacological activities,pharmacokinetics,toxicology,and structure-activity relationship,as well as the future research directions of the extractive for further development and utilization of A.lappa.展开更多
A series of nano-size gold catalysts were prepared by deposition-precipitation method using silica material promoted with different amounts of MgO as the carrier. The influences of MgO addition on the structure and pr...A series of nano-size gold catalysts were prepared by deposition-precipitation method using silica material promoted with different amounts of MgO as the carrier. The influences of MgO addition on the structure and property of the nano-size gold catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), O2 temperature-programmed desorption (O2-TPD), and inductively coupled with plasma atomic emission spectroscopy (ICP-AES) techniques. The total oxidation of CO was chosen as the probe reaction. The results suggest that for the gold catalysts supported on the silica material after MgO modification, the size of the gold particles is pronouncedly reduced, the oxygen mobility is enhanced, and the catalytic activity for low-temperature CO oxidation is greatly improved. The gold catalyst modified by 6 wt% MgO (Mg/SiO2 weight ratio) shows higher CO oxidation activity, over which the temperature of CO total oxidation is lower about 150 K than that over the silica directly supported gold catalyst.展开更多
In this study,different methods of variable selection using the multilinear step-wise regression(MLR) and support vector regression(SVR) have been compared when the performance of genetic algorithms(GAs) using v...In this study,different methods of variable selection using the multilinear step-wise regression(MLR) and support vector regression(SVR) have been compared when the performance of genetic algorithms(GAs) using various types of chromosomes is used.The first method is a GA with binary chromosome(GA-BC) and the other is a GA with a fixed-length character chromosome(GA-FCC).The overall prediction accuracy for the training set by means of 7-fold cross-validation was tested.All the regression models were evaluated by the test set.The poor prediction for the test set illustrates that the forward stepwise regression(FSR) model is easier to overfit for the training set.The results using SVR methods showed that the over-fitting could be overcome.Further,the over-fitting would be easier for the GA-BC-SVR method because too many variables fleetly induced into the model.The final optimal model was obtained with good predictive ability(R2 = 0.885,S = 0.469,Rcv2 = 0.700,Scv = 0.757,Rex2 = 0.692,Sex = 0.675) using GA-FCC-SVR method.Our investigation indicates the variable selection method using GA-FCC is the most appropriate for MLR and SVR methods.展开更多
A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitativ...A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitative structure-activity relationship(QSAR)model of toxicity(–lgEC50)was obtained through multiple linear regression(MLR)and stepwise multiple regression(SMR).The correlation coefficient(R)of the model was 0.912,and the standard deviation(SD)of the model was 0.525.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The Leave-One-Out(LOO)Cross-Validation(CV)correlation coefficient(RCV)was 0.816 and the standard deviation(SDCV)was 0.739,respectively.For the external validation,the correlation coefficient(Rtest)was 0.905 and the standard deviation(SDtest)was 0.520,respectively.The results showed that the index was superior in molecular structural representation.The stability and predictability of the model were good.展开更多
Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogen...Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling" published in Nature journal on inactivating the kinase suppressor of Ras(KSR) protein using a small molecule as an inhibitor by Dhawan et al. A biphenyl ether analogue of a quinazoline binds in one of the binding pockets of KSR and results in stabilization of its inactive state. In this inactive state, KSR is unable to take part in the cascade of protein association to perform the signalling process.展开更多
基金supported by National Council for Scientific and Technological Development (CNPq)Coordenao de Aperfeioamento de Pessoal de Nível Superior (CAPES)+1 种基金Oswaldo Cruz Foundation (Fiocruz)Department of Science and Technology,New Delhi,India [No.SR/WOS-A/LS-562/2011) dated 27/03/2012]
文摘Platinum containing compounds have shown antineoplastic potential, but their clinical applications have been limited by high toxicity. Ruthenium containing complexes have long been known to be well suited for biological applications, and have long been utilized as replacements to popular platinum based-drugs. Here, we report a novel series of ruthenium(ll) arene compounds bearing thiosemicarba- zone and isonicotinylhydrazone ligands with potent anticancer activity their structure activity relationships and apoptosis was studied. The cytotoxic activity of the new ruthenium(ll) arene compounds has been evaluated in several cell lines (Molt 4/C8, LI 210, CEM, HL60 and BEL7402). Among them, ten complexes were found to be excellent in vitro growth inhibitory activity against various cell lines with IC50 in the sub-micromolar range.
基金supported by the National Natural Science Foundation of China(U1905202,31972017,and 31771922)the National Key R&D Program of China(2018YFD0901006)+2 种基金the Fujian Major Project of Provincial Science&Technology Hall,China(2020NZ010008)the Open Project of the Key Laboratory of Refrigeration and Conditioning Aquatic Products Processing,Ministry of Agriculture and Rural Affairs,China(KLRCAPP2021-03)the Quanzhou Science&Technology Project,China(2019C085R)。
文摘Peptides are functional active fragments of proteins which can provide nutrients needed for human growth and development,and they also have unique physiological activity characteristics relative to proteins.Bioactive peptides contain a great deal of development potential.More specifically,food-derived bioactive peptides have the advantages of a wide variety of sources,unique structures,high efficiency and safety,so they have broad development prospects.This review provides an overview of the current advances regarding the preparation,functional characteristics,and structure–activity relationships of food-derived bioactive peptides.Moreover,the prospects for the future development and application of food-derived bioactive peptides are discussed.This review may provide a better understanding of foodderived bioactive peptides,and some constructive inspirations for further research and applications in the food industry.
文摘A method for the analysis of the relationship between the helical structure and optical activity was proposed by the study of the conformations and X-ray diffraction structures of some cyclic esters prepared by esterification of L-(-)-2.3-O-methylidene threitol and L-(+)-2,3-O-isopropplidene threitol with alkanedioyl dichlorides and o-,m-,and p-phthaloyl dichlorides.
基金This research was supported by the National Natural Science Foundation of China (No. 81273537), Scientific Research Fund of Education Department of Hunan Province (No. 17A190), the Key Project of Science and Technology Department of Hunan Province (No. 2016DK2001), and the Key Disciplines of Hunan Province and the Zhengxing Scholar Program of the University of South China.
文摘Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.
基金the National Natural Science Foundation of China(No.32272575)National College Student Innovation and Entrepreneurship Training Program(No.202210459164)for financial support.
文摘Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.
基金financially supported by the National Natural Science Foundation of China(Nos.82104281,81922070,81973286,81801818 and 82273897)Shanghai Municipal Health Commission’s TCM research project(No.2022CX005)+1 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[No.ZY(2021–2023)-0401]。
文摘Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.
基金financially sponsored by the National Natural Science Foundation of China(Grant Nos.22075223,22179104)the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(2022-ZD-4)。
文摘Precisely tuning the spacing of the active centers on the atomic scale is of great significance to improve the catalytic activity and deepen the understanding of the catalytic mechanism,but still remains a challenge.Here,we develop a strategy to dilute catalytically active metal interatomic spacing(d_(M-M))with light atoms and discover the unusual adsorption patterns.For example,by elevating the content of boron as interstitial atoms,the atomic spacing of osmium(d_(Os-Os))gradually increases from 2.73 to 2.96?.More importantly,we find that,with the increase in dOs-Os,the hydrogen adsorption-distance relationship is reversed via downshifting d-band states,which breaks the traditional cognition,thereby optimizing the H adsorption and H_2O dissociation on the electrode surface during the catalytic process;this finally leads to a nearly linear increase in hydrogen evolution reaction activity.Namely,the maximum dOs-Os of 2.96?presents the optimal HER activity(8 mV@10 mA cm^(-2))in alkaline media as well as suppressed O adsorption and thus promoted stability.It is believed that this novel atomic-level distance modulation strategy of catalytic sites and the reversed hydrogen adsorption-distance relationship can shew new insights for optimal design of highly efficient catalysts.
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
文摘A series of trihydrocarbyltin chlorides containing silicon was synthesized. The acaricidal activity was determined and the structure activity relationship was tried to be found out with the hydrophobic parameter.
基金supported by two grants(UIC202007 and UIC202107)from BNU-HKBU United International College.
文摘The isolated secondary metabolites from 39 edible mushrooms are reported,among which 107 compounds were active,61 demonstrated antitubercular activities with IC_(50) range of 0.2-50μg/mL and 46 manifested antimalarial effects with IC_(50) range of 0.061-36μg/mL.While more than 2000 strains of edible mushrooms are identified,this review shows the paucity of research in these rich organisms featuring a vital culinary ingredient worldwide.A thorough search was conducted on basidiomycetes to discuss the chemistry and biology of the isolated compounds,structure activity relationships(SAR)as well as the cytotoxicity profiles of,primarily,the active anti-plasmodial and antitubercular molecules.With a safe cellular profile,lanostane triterpenoids were found to be the only molecules with combined activities against both diseases.SAR correlations reviewed here indicated the significance of 3β-and 7α-hydroxylation in the anti-tuberculosis activity and the terminal unsaturated moiety between C-4 and C-28 in the antimalarial activity in the same terpene skeleton.This review will attract the attention of medicinal chemists,and food scientists to optimize and rationalize the use of mushrooms both as unexploited sources of novel molecules and as nutraceuticals to treat two of the deadliest infectious diseases,malaria,and tuberculosis.
文摘Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as antioxidant,anti-tumor,anti-microbial and anti-inflammatory activities.It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system.Recently,the pharmacological validation on immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity.In this review,we have highlighted several studies on immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models.This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship.Hence,the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial immunomodulatory properties.
基金financially supported by the National Natural Science Foundation of China(No.51074037)
文摘Effects of carboxylic acid collector, benzohydroxamic acid (BHA), sodium hexametaphosphate (SHAP), sodium silicate, and oxalic acid on scheelite flotation were studied through flotation tests, quantum chemical calculation, and flotation solution computational chemistry. In terms of the calculation results, the relationship between chemical reactions occurring on the scheelite surface and molecular structures of the reagents were analyzed. The results show that BHA and carboxylic acid collectors interact with scheelite in different forms and the recovery of scheelite using sodium oleate as collector declines successively from SHAP, sodium silicate, to oxalic acid. Moreover, it is found that the performance of depressant in scheelite flotation is directly related to the group electronegativity, indicating that the latter is a dominant factor that determines the former. These findings will be helpful to the academic research communities of scheelite flotation.
基金We thank Prof.Junying Yuan(IRCBC of CAS,Shanghai,China)and Dr.Jidong Zhu(Etern Therapeutics,Shanghai,China)for their generous help on this work,Dr.Sudan He(ISM of CAMS,Suzhou,China)for providing RIPK3-FKBP NIH/3T3 cells,and National Facility for Protein Science in Shanghai(China)for the help in animal studies.This work was supported by grants from the National Natural Science Foundation of China(Grants Nos.21837004,82151212,and 32170755)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39050500,China)Shanghai Municipal Science and Technology Major Project(Grant No.2019SHZDZX02,China).
文摘Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.
文摘C-glycosylflavonoids are characterized by a bond between the anomeric carbon of a sugar moiety and the C-6 or C-8 position of a flavonoid A ring.These compounds are widespread in nature and have become the subject of increasing research interest due to their high biological potential.This review focuses on the biological effects of various C-glycosylflavonoids and their structure–activity relationships(SAR)as elucidated over the last 5 years.
基金supported by Special Financial Grant from the China Postdoctoral Science Foundation (No.2015T81140)National Natural Science Foundation of China Youth Fund Project (No.81503467)。
文摘The medicinal part of Aucklandia lappa(Asteraceae) is its dried root,which is one of the commonly used Chinese medicinal materials.Here we reviewed sesquiterpene lactones isolated from A.lappa over the past ten years in the following aspects of pharmacological activities,pharmacokinetics,toxicology,structure-activity relationship.Pharmacological activities consist of anti-cancer,anti-inflammatory activity,anti-immunity activity,anti-oxidant activity,antimicrobial activity,spasmolytic activity and so on.The extractive,showing similar pharmacokinetics parameters,may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition.However,the poor aqueous solubility,non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class.In order to evaluate the potential effect of the extractive applied in clinical trial,the present review outlines information on pharmacological activities,pharmacokinetics,toxicology,and structure-activity relationship,as well as the future research directions of the extractive for further development and utilization of A.lappa.
基金supported by the Youth Fund Project(2002B25)of Sichuan Department of Educationthe Scientific Research Foundation for Doctor from Yibin College of China(2010B12)
文摘A series of nano-size gold catalysts were prepared by deposition-precipitation method using silica material promoted with different amounts of MgO as the carrier. The influences of MgO addition on the structure and property of the nano-size gold catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), O2 temperature-programmed desorption (O2-TPD), and inductively coupled with plasma atomic emission spectroscopy (ICP-AES) techniques. The total oxidation of CO was chosen as the probe reaction. The results suggest that for the gold catalysts supported on the silica material after MgO modification, the size of the gold particles is pronouncedly reduced, the oxygen mobility is enhanced, and the catalytic activity for low-temperature CO oxidation is greatly improved. The gold catalyst modified by 6 wt% MgO (Mg/SiO2 weight ratio) shows higher CO oxidation activity, over which the temperature of CO total oxidation is lower about 150 K than that over the silica directly supported gold catalyst.
基金supported by Youth Foundation of the Education Department of Sichuan Province (No.09ZB038)
文摘In this study,different methods of variable selection using the multilinear step-wise regression(MLR) and support vector regression(SVR) have been compared when the performance of genetic algorithms(GAs) using various types of chromosomes is used.The first method is a GA with binary chromosome(GA-BC) and the other is a GA with a fixed-length character chromosome(GA-FCC).The overall prediction accuracy for the training set by means of 7-fold cross-validation was tested.All the regression models were evaluated by the test set.The poor prediction for the test set illustrates that the forward stepwise regression(FSR) model is easier to overfit for the training set.The results using SVR methods showed that the over-fitting could be overcome.Further,the over-fitting would be easier for the GA-BC-SVR method because too many variables fleetly induced into the model.The final optimal model was obtained with good predictive ability(R2 = 0.885,S = 0.469,Rcv2 = 0.700,Scv = 0.757,Rex2 = 0.692,Sex = 0.675) using GA-FCC-SVR method.Our investigation indicates the variable selection method using GA-FCC is the most appropriate for MLR and SVR methods.
基金supported by the Foundation of Education Bureau,Sichuan Province (09ZB036)Technology Bureau,Sichuan Province (2006j13-141)
文摘A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitative structure-activity relationship(QSAR)model of toxicity(–lgEC50)was obtained through multiple linear regression(MLR)and stepwise multiple regression(SMR).The correlation coefficient(R)of the model was 0.912,and the standard deviation(SD)of the model was 0.525.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The Leave-One-Out(LOO)Cross-Validation(CV)correlation coefficient(RCV)was 0.816 and the standard deviation(SDCV)was 0.739,respectively.For the external validation,the correlation coefficient(Rtest)was 0.905 and the standard deviation(SDtest)was 0.520,respectively.The results showed that the index was superior in molecular structural representation.The stability and predictability of the model were good.
文摘Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling" published in Nature journal on inactivating the kinase suppressor of Ras(KSR) protein using a small molecule as an inhibitor by Dhawan et al. A biphenyl ether analogue of a quinazoline binds in one of the binding pockets of KSR and results in stabilization of its inactive state. In this inactive state, KSR is unable to take part in the cascade of protein association to perform the signalling process.