The antagonistic activity of Lactobacillus acidophilus KLDS1.0901, KLDS1.0902, KLDSI.1003 and NCFM against Escherichia coli O157 : H7 were investigated in this study. The culture supematants of all the L. acidophilus...The antagonistic activity of Lactobacillus acidophilus KLDS1.0901, KLDS1.0902, KLDSI.1003 and NCFM against Escherichia coli O157 : H7 were investigated in this study. The culture supematants of all the L. acidophilus stains showed high bacteriostatic activities against E. coli O 157 : H7 and the bacteriostatic substances of their Cell-Free Supernatants (CFS) were preliminarily determined from organic acids. The bacteriostatic activity from CFS or viable L. acidophilus against E. coli O157 : H7 was also assessed by using co-incubation methods, CFS had high bactericidal activity against E. coli O157 : H7, no viable E. coli O157 : H7 was detected when 5×10^7 CfU ofE. coli O157 : H7 was added to 5 mL of CFS and incubated at 37℃ for 2 h. However, L. acidophilus themselves had no bacteriostatic activity after directly contacted with E. coli O157 : H7. The inhibition E. coli O157 : H7 adhesion and colonization of L. acidophilus were also investigated based on competition, exclusion and displacement assays. L. acidophilus KLDS1.0901, KLDSI.1003 and NCFM strains were effective to displace E. coli O157 : H7 from a Caco-2 cell layer in competition and exclusion assays. However, in displacement assay, all of the strains showed no significant antagonistic activities. Meanwhile, the probiotic potential of L. acidophilus strains was investigated based on adhesion assay to Caco-2 cells and anti- inflammatory effects by IL-8 produced in Caco-2 cells. The adhesion ability and anti-inflammatory effects of L. acidophilus strains showed a strain-dependent manner. In general, L. acidophilus KLDS 1.0901 and NCFM showed better probiotic potential than KLDS1.0902 and KLDSI.1003. Thus, the use ofL. acidophilus KLDS1.0901 and NCFM to prevent or treat of diseases associated induced E. coli O157 : H7 in vivo was suggested.展开更多
Prediction of antagonistic activity of <em>β</em>-carboline and its thirteen derivatives has been made using topological descriptors viz, connectivity index, and kappa shape index of different orders. For...Prediction of antagonistic activity of <em>β</em>-carboline and its thirteen derivatives has been made using topological descriptors viz, connectivity index, and kappa shape index of different orders. For evaluation of values of descriptor, molecular modeling and geometry optimization of all the compounds were carried out with CAChe Pro software by opting semiempirical PM3 method using MOPAC 2002. For prediction of activity multiple linear regression analysis (MLR) was performed. MLR analysis has been made by Project Leader Software associated with CAChe by using the above descriptors as independent variables and biological activity as dependent variables. We were performed leave-one-out methods and the result reflected a direct relationship between biological activity and connectivity index of zero order, while indirect relationship with connectivity index of second order and thus connectivity index is a reliable descriptor to predict the biological activity of <em>β</em>-carboline and its various derivatives.展开更多
One hundred twenty-five endophytic microorganisms were isolated from the roots,stems,and leaves of four prominent rice cultivars growing in temperate regions.Their potential to combat rice blast disease and promote pl...One hundred twenty-five endophytic microorganisms were isolated from the roots,stems,and leaves of four prominent rice cultivars growing in temperate regions.Their potential to combat rice blast disease and promote plant growth was investigated.The dual culture tests highlighted the strong antagonistic activity of five fungal(ranging from 89%–70%)and five bacterial(72%–61%)endophytes.Subsequent examination focused on volatile compounds produced by selected isolates to counter the blast pathogen.Among these,the highest chitinase(13.76μg mL−1)and siderophore(56.64%),was exhibited by Aspergillus flavus,and the highest HCN production was shown by Stenotrophomonas maltophilia(36.15μM mL−1).In terms of growth promotion traits,Aspergillus flavus and Enterobacter cloacae excelled in activities viz,phosphorous solubilization,ammonia production,auxin and gibberellic acid production,and nitrogen fixation.The Identity of these endophytes was confirmed through molecular analysis as Trichoderma afroharzianum,Trichoderma harzianum,Penicillium rubens,Aspergillus flavus,Stenotrophomonas rhizophila,Stenotrophomonas maltophilia,Bacillus cereus,Enterobacter cloacae,and Bacillus licheniformis.Under greenhouse conditions,the highest disease control was shown by isolate Bacillus licheniformis and A.flavus with an inhibition of 79%,followed by S.rhizophila(77%)and T.afroharzianum(73%).The overall results of this study showed that Bacillus licheniformis and Stenotrophomonas rhizophila have great potential to be used as bio-stimulant and biocontrol agents to manage rice blast disease.展开更多
Objective:To compare the phytochemical and antimicrobial activity of Ethiopian Kale leaves infusions,investigate the antioxidant activity and profile the major phytochemicals existing in the better solvent system.Meth...Objective:To compare the phytochemical and antimicrobial activity of Ethiopian Kale leaves infusions,investigate the antioxidant activity and profile the major phytochemicals existing in the better solvent system.Methods:Ethiopian Kale leaves were collected from Addis Ababa,Ethiopia,and extracted using different solvents.The qualitative phytochemical analysis,antibacterial assays,and Fourier Transform Infrared(FTIR) analysis are executed for all extracts.Antioxidant assay and Gas Chromatography-Mass Spectrometry(GC-MS) analysis are carried out for the solvent system,which showed better activity in preliminary studies.Results:The qualitative phytochemical analysis exposed the presence of different classes of phytoconstituents in most of the tested extracts.The broad spectrum of antibacterial activity(7-15 mm) was noted against the tested bacterial species.The functional groups of the extracts are reported by FTIR analysis.The antioxidant ability of ethanol extract was found to be(62.92±0.34)% for 2,2-diphenyl-1-picrylhydrazyl(DPPH*) assay and(71.12±0.41)% for 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) assay.More than 17 major phytocompounds in ethanol extract were profiled by GC-MS analysis.Conclusion:The ethanol extract of Ethiopian Kale leaves contain a good source of phytochemicals and it can be a significant source for various functional applications.展开更多
Objective:To investigate the in vivo efficacy and immune-modulatory potential of antagonistic strain,Streptomyces sp.MAPS15 isolated from marine sponge in Penaeus monodon(P.monodon).Methods:In this study,culture of St...Objective:To investigate the in vivo efficacy and immune-modulatory potential of antagonistic strain,Streptomyces sp.MAPS15 isolated from marine sponge in Penaeus monodon(P.monodon).Methods:In this study,culture of Streptomyces sp.was incorporated into a commercial feed.P.monodon was orally administered with MAPS15 diet for a period of 21 days followed by a challenge experiment and survival rate was calculated.In addition,the effect of MAPS15 diet on immunological parameters of the haemolymph of P.monodon was also assessed.Results:The overall results of the study showed that survival performance was prominent in MAPS15 treated group when compared with un-treated control groups.That could pertain to the ability of MAPS15 to produce antibiotic compounds to suppress the growth of invading pathogens and thereby increase the disease resistance potency and survival rate.From the results of the immunological studies,it can be envisaged that the immune responses were generally more pronounced with MAPS15 diet treated group.Conclusions:Based on the overall findings,it could be inferred that the health of P.monodon is improved when they are fed with MAPS15 diet for a period of 21 days.展开更多
Soil salinization affecting different crops is one of the serious threats to global food security.Soil salinity affects 20%and 33%of the total cultivated and irrigated agricultural lands,respectively,and has been repo...Soil salinization affecting different crops is one of the serious threats to global food security.Soil salinity affects 20%and 33%of the total cultivated and irrigated agricultural lands,respectively,and has been reported to caused a global crop production loss of 27.3 billion USD.The conventional approaches,such as using salt-tolerant varieties,saline soil scrapping,flushing,leaching,and adding supplements (e.g.,gypsum and lime),often fail to alleviate stress.In this context,developing diverse arrays of microbes enhancing crop productivity under saline soil conditions without harming soil health is necessary.Various advanced omics approaches have enabled gaining new insights into the structure and metabolic functions of plant-associated beneficial microbes.Various genera of salt-tolerating rhizobacteria ameliorating biotic and abiotic stresses have been isolated from different legumes,cereals,vegetables,and oil seeds under extreme alkaline and saline soil conditions.Rapid progress in rhizosphere microbiome research has revived the belief that plants may be more benefited from their association with interacting diverse microbial communities as compared with individual members in a community.In the last decade,several salt-tolerating plant growth-promoting rhizobacteria (PGPR) that improve crop production under salt stress have been exploited for the reclamation of saline agrosystems.This review highlights that the interaction of salt-tolerating microbes with plants improves crop productivity under salinity stress along with potential salt tolerance mechanisms involved and will open new avenues for capitalizing on cultivable diverse microbial communities to strengthen plant salt tolerance and,thus,to refine agricultural practices and production under saline conditions.展开更多
Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities w...Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.展开更多
Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy...Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. Methods Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. Results Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preec^ampsia patients. In particular, intedeukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. Conclusions Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.展开更多
A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine...A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.展开更多
The structure–activity relationship(SAR) study of a 1 2 3 4 4a 9a-hexahydro-1H-xanthene series of selective,human glucocorticoid receptor a(hGRa) antagonists is reported.Compounds were screened using hydroxyapati...The structure–activity relationship(SAR) study of a 1 2 3 4 4a 9a-hexahydro-1H-xanthene series of selective,human glucocorticoid receptor a(hGRa) antagonists is reported.Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays.Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency.Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a,as well as an improved chemical stability,which make it a promising lead for the subsequent optimization.展开更多
基金Supported by the Agro-scientific Research of China(201203009)the Ministry of Agriculture,China
文摘The antagonistic activity of Lactobacillus acidophilus KLDS1.0901, KLDS1.0902, KLDSI.1003 and NCFM against Escherichia coli O157 : H7 were investigated in this study. The culture supematants of all the L. acidophilus stains showed high bacteriostatic activities against E. coli O 157 : H7 and the bacteriostatic substances of their Cell-Free Supernatants (CFS) were preliminarily determined from organic acids. The bacteriostatic activity from CFS or viable L. acidophilus against E. coli O157 : H7 was also assessed by using co-incubation methods, CFS had high bactericidal activity against E. coli O157 : H7, no viable E. coli O157 : H7 was detected when 5×10^7 CfU ofE. coli O157 : H7 was added to 5 mL of CFS and incubated at 37℃ for 2 h. However, L. acidophilus themselves had no bacteriostatic activity after directly contacted with E. coli O157 : H7. The inhibition E. coli O157 : H7 adhesion and colonization of L. acidophilus were also investigated based on competition, exclusion and displacement assays. L. acidophilus KLDS1.0901, KLDSI.1003 and NCFM strains were effective to displace E. coli O157 : H7 from a Caco-2 cell layer in competition and exclusion assays. However, in displacement assay, all of the strains showed no significant antagonistic activities. Meanwhile, the probiotic potential of L. acidophilus strains was investigated based on adhesion assay to Caco-2 cells and anti- inflammatory effects by IL-8 produced in Caco-2 cells. The adhesion ability and anti-inflammatory effects of L. acidophilus strains showed a strain-dependent manner. In general, L. acidophilus KLDS 1.0901 and NCFM showed better probiotic potential than KLDS1.0902 and KLDSI.1003. Thus, the use ofL. acidophilus KLDS1.0901 and NCFM to prevent or treat of diseases associated induced E. coli O157 : H7 in vivo was suggested.
文摘Prediction of antagonistic activity of <em>β</em>-carboline and its thirteen derivatives has been made using topological descriptors viz, connectivity index, and kappa shape index of different orders. For evaluation of values of descriptor, molecular modeling and geometry optimization of all the compounds were carried out with CAChe Pro software by opting semiempirical PM3 method using MOPAC 2002. For prediction of activity multiple linear regression analysis (MLR) was performed. MLR analysis has been made by Project Leader Software associated with CAChe by using the above descriptors as independent variables and biological activity as dependent variables. We were performed leave-one-out methods and the result reflected a direct relationship between biological activity and connectivity index of zero order, while indirect relationship with connectivity index of second order and thus connectivity index is a reliable descriptor to predict the biological activity of <em>β</em>-carboline and its various derivatives.
基金The authors extend their appreciation to the Researchers Supporting Project Number(RSP2023R298),King Saud University,Riyadh,Saudi Arabia.
文摘One hundred twenty-five endophytic microorganisms were isolated from the roots,stems,and leaves of four prominent rice cultivars growing in temperate regions.Their potential to combat rice blast disease and promote plant growth was investigated.The dual culture tests highlighted the strong antagonistic activity of five fungal(ranging from 89%–70%)and five bacterial(72%–61%)endophytes.Subsequent examination focused on volatile compounds produced by selected isolates to counter the blast pathogen.Among these,the highest chitinase(13.76μg mL−1)and siderophore(56.64%),was exhibited by Aspergillus flavus,and the highest HCN production was shown by Stenotrophomonas maltophilia(36.15μM mL−1).In terms of growth promotion traits,Aspergillus flavus and Enterobacter cloacae excelled in activities viz,phosphorous solubilization,ammonia production,auxin and gibberellic acid production,and nitrogen fixation.The Identity of these endophytes was confirmed through molecular analysis as Trichoderma afroharzianum,Trichoderma harzianum,Penicillium rubens,Aspergillus flavus,Stenotrophomonas rhizophila,Stenotrophomonas maltophilia,Bacillus cereus,Enterobacter cloacae,and Bacillus licheniformis.Under greenhouse conditions,the highest disease control was shown by isolate Bacillus licheniformis and A.flavus with an inhibition of 79%,followed by S.rhizophila(77%)and T.afroharzianum(73%).The overall results of this study showed that Bacillus licheniformis and Stenotrophomonas rhizophila have great potential to be used as bio-stimulant and biocontrol agents to manage rice blast disease.
基金Addis Ababa Science and Technology University, Ethiopia for providing partial financial support (Grant Reference No-AASTU-SSRF-CBCE-BT-2018)。
文摘Objective:To compare the phytochemical and antimicrobial activity of Ethiopian Kale leaves infusions,investigate the antioxidant activity and profile the major phytochemicals existing in the better solvent system.Methods:Ethiopian Kale leaves were collected from Addis Ababa,Ethiopia,and extracted using different solvents.The qualitative phytochemical analysis,antibacterial assays,and Fourier Transform Infrared(FTIR) analysis are executed for all extracts.Antioxidant assay and Gas Chromatography-Mass Spectrometry(GC-MS) analysis are carried out for the solvent system,which showed better activity in preliminary studies.Results:The qualitative phytochemical analysis exposed the presence of different classes of phytoconstituents in most of the tested extracts.The broad spectrum of antibacterial activity(7-15 mm) was noted against the tested bacterial species.The functional groups of the extracts are reported by FTIR analysis.The antioxidant ability of ethanol extract was found to be(62.92±0.34)% for 2,2-diphenyl-1-picrylhydrazyl(DPPH*) assay and(71.12±0.41)% for 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) assay.More than 17 major phytocompounds in ethanol extract were profiled by GC-MS analysis.Conclusion:The ethanol extract of Ethiopian Kale leaves contain a good source of phytochemicals and it can be a significant source for various functional applications.
基金Supported by Department of Scientific and Industrial Research,New Delhi
文摘Objective:To investigate the in vivo efficacy and immune-modulatory potential of antagonistic strain,Streptomyces sp.MAPS15 isolated from marine sponge in Penaeus monodon(P.monodon).Methods:In this study,culture of Streptomyces sp.was incorporated into a commercial feed.P.monodon was orally administered with MAPS15 diet for a period of 21 days followed by a challenge experiment and survival rate was calculated.In addition,the effect of MAPS15 diet on immunological parameters of the haemolymph of P.monodon was also assessed.Results:The overall results of the study showed that survival performance was prominent in MAPS15 treated group when compared with un-treated control groups.That could pertain to the ability of MAPS15 to produce antibiotic compounds to suppress the growth of invading pathogens and thereby increase the disease resistance potency and survival rate.From the results of the immunological studies,it can be envisaged that the immune responses were generally more pronounced with MAPS15 diet treated group.Conclusions:Based on the overall findings,it could be inferred that the health of P.monodon is improved when they are fed with MAPS15 diet for a period of 21 days.
文摘Soil salinization affecting different crops is one of the serious threats to global food security.Soil salinity affects 20%and 33%of the total cultivated and irrigated agricultural lands,respectively,and has been reported to caused a global crop production loss of 27.3 billion USD.The conventional approaches,such as using salt-tolerant varieties,saline soil scrapping,flushing,leaching,and adding supplements (e.g.,gypsum and lime),often fail to alleviate stress.In this context,developing diverse arrays of microbes enhancing crop productivity under saline soil conditions without harming soil health is necessary.Various advanced omics approaches have enabled gaining new insights into the structure and metabolic functions of plant-associated beneficial microbes.Various genera of salt-tolerating rhizobacteria ameliorating biotic and abiotic stresses have been isolated from different legumes,cereals,vegetables,and oil seeds under extreme alkaline and saline soil conditions.Rapid progress in rhizosphere microbiome research has revived the belief that plants may be more benefited from their association with interacting diverse microbial communities as compared with individual members in a community.In the last decade,several salt-tolerating plant growth-promoting rhizobacteria (PGPR) that improve crop production under salt stress have been exploited for the reclamation of saline agrosystems.This review highlights that the interaction of salt-tolerating microbes with plants improves crop productivity under salinity stress along with potential salt tolerance mechanisms involved and will open new avenues for capitalizing on cultivable diverse microbial communities to strengthen plant salt tolerance and,thus,to refine agricultural practices and production under saline conditions.
基金project was supported by National 973 Plan(Nos. 2010CB735602 and 2012CB724002)National Major Scientific and Technological Special Project for "Significant New Drugs Development"(No.2011ZX09401-009)
文摘Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.
基金This study was supported by grants from the National Natural Science Foundation of China,Science and Technology Bureau of Sichuan Province,Science and Technology Development of Chengdu City
文摘Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. Methods Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. Results Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preec^ampsia patients. In particular, intedeukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. Conclusions Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.
基金supported by National Major Scientific and Technological Special Project for "Significant New Drugs Development"(Nos.2011ZX09401-009 and 2013ZX09102014)
文摘A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.
基金supported in part by grants from the Ministry of Health of China (Nos. 2012ZX09304-011, 2013ZX09401003-005, 2013ZX09507001 and 2013ZX09507002)Shanghai Science and Technology Development Fund (No. 13DZ2290300)Thousand Talents Program in China
文摘The structure–activity relationship(SAR) study of a 1 2 3 4 4a 9a-hexahydro-1H-xanthene series of selective,human glucocorticoid receptor a(hGRa) antagonists is reported.Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays.Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency.Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a,as well as an improved chemical stability,which make it a promising lead for the subsequent optimization.