Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,rema...Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.展开更多
Bacterial species of the genus Lysobacter are environmentally ubiquitous with strong antifungal biocontrol potential.Heat-stable antifungal factor(HSAF)secreted by the biocontrol bacterium Lysobacter enzymogenes OH11 ...Bacterial species of the genus Lysobacter are environmentally ubiquitous with strong antifungal biocontrol potential.Heat-stable antifungal factor(HSAF)secreted by the biocontrol bacterium Lysobacter enzymogenes OH11 has broad-spectrum and highly efficient antifungal activity.Studying the biosynthetic regulations of HSAF would lay an important foundation for strain engineering toward improved HSAF production.In this work,we demonstrate that Le0752,an orotidine-5´-phosphate decarboxylase enzyme(ODCase)catalyzing a pivotal step of the UMP de novo biosynthesis pathway,is vital for HSAF-mediated antimicrobial activities and growth of L.enzymogenes OH11,but not for twitching motility.This gene regulates the production of HSAF by affecting the expression of lafB,a key gene in the HSAF biosynthesis operon,through the transcription factor Clp.Interestingly,bioinformatics analysis revealed that Le0752 belongs to the Group III ODCases,whereas its homologs in the closely related genera Xanthomonas and Stenotrophomonas belong to Group I,which contains most ODCases from Gram-positive bacteria,Gram-negative bacteria and cyanobacteria.Moreover,the Group I ODCase PXO_3614 from the Xanthomonas oryzae pv.oryzae PXO99A strain complemented the Le0752 mutant in regulating HSAF-mediated antagonistic activity.Together,these results highlight the important requirement of de novo pyrimidine biosynthetic enzymes for antibiotic HSAF production in L.enzymogenes,which lays an important foundation for improving HSAF production via metabolic flow design and for dissecting the regulatory functions of bacterial ODCases.展开更多
Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent pr...Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.展开更多
A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidine...A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.展开更多
Five rice ( Oryza sativa L.) cultivars, widely planted in South China, were grown in greenhouse with or without supplemental UV_B radiation at level of 13.6 kJ·m -2 ·d -1 . After 15 day_UV_B treat...Five rice ( Oryza sativa L.) cultivars, widely planted in South China, were grown in greenhouse with or without supplemental UV_B radiation at level of 13.6 kJ·m -2 ·d -1 . After 15 day_UV_B treatment, significant intraspecific differences were observed in plant height, photosynthetic rate and total biomass. Based on the total biomass accumulation, cultivar “Tesanai” was found to be the most sensitive, and cultivar “Luhuangzhan” was the most tolerant species to UV_B radiation. UV_B induced cyclobutane pyrimidine dimer (CPD) in rice DNA were quantified by ELISA with specific monoclonal antibody. CPD accumulations in DNA extracted from 5 rice cultivars were remarkably increased by UV_B radiation, and it was confirmed that there was a strong positive correlation between CPD accumulation and the inhibition of total biomass. Photorepair was proved to be the predominant mode of CPD repair in UV_B irradiated rice. Light_dependent removal of CPD was very fast as compared with dark repair. Different levels of CPD accumulation among rice cultivars were related with different capacity of CPD photorepair. Capacity of light_dependent CPD removal may play an important role in UV_B resistance of rice.展开更多
Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotsch...Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotschibabin reaction of a-bromoacetophenones with 2-aminopyrimidine in good yields.展开更多
Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malo...Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.展开更多
The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of ...The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of the target compound, we report its crystal structure and herbi- cidal behavior in the present paper. Crystallographic data: C15H12N4O4Cl2S, Mr = 415.25, mono- clinic, space group P21/n, a = 10.7361(8), b = 11.9610(9), c = 13.0990(10) ?, β = 96.988(2)o, Z = 4, V = 1669.6(2) ?3, Dc = 1.652 g/cm3, F(000) = 848, R = 0.0394, wR = 0.0797 and μ(MoKα) = 0.545 mm-1.展开更多
The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of ...The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of the target compound, we report its crystal structure and herbi- cidal behavior in the present paper. Crystallographic data: C15H12N4O4Cl2S, Mr = 415.25, mono- clinic, space group P21/n, a = 10.7361(8), b = 11.9610(9), c = 13.0990(10) ?, β = 96.988(2)o, Z = 4, V = 1669.6(2) ?3, Dc = 1.652 g/cm3, F(000) = 848, R = 0.0394, wR = 0.0797 and μ(MoKα) = 0.545 mm-1.展开更多
2-Aminocyclopenta[d]pyrimidines 3a-c were achieved via a one-pot, three-component reactions of cyclopentanone 1, aromatic aldehyde and guanidine hydrochloride （1：2：1 molar ratio）. Also, cyclization of 2,5-bis-（ar...2-Aminocyclopenta[d]pyrimidines 3a-c were achieved via a one-pot, three-component reactions of cyclopentanone 1, aromatic aldehyde and guanidine hydrochloride （1：2：1 molar ratio）. Also, cyclization of 2,5-bis-（arylmethylidene）cyclopentanones 2 with guanidine hydrochloride （1：1 molar ratio） in methanol in the presence of sodium methoxide afforded cyclopenta-[d]pyrimidines 3. Compound 3c has been shown to be a useful building block for the synthesis of some novel pyrimido[ 1,2-a]pyrimidines 5, 7 and 12. The structures of the newly synthesized compounds were confirmed on the basis of analytical and spectral data,展开更多
Four novel pyridimine compounds were prepared. The yield of the intermediates was improved with new method making use of Pd(Ⅱ) catalyst and cuprous acetylide which were proved to be practital in the formation of the ...Four novel pyridimine compounds were prepared. The yield of the intermediates was improved with new method making use of Pd(Ⅱ) catalyst and cuprous acetylide which were proved to be practital in the formation of the acetylide which were proved to be practical in the formation of the acetylides. Their nonlinear optical properties were briefly studied.展开更多
The importance of pyrimidines lies in the fact that they are structural components of a broad spectrum of key molecules that participate in diverse cellular functions, such as synthesis of DNA, RNA, lipids, and carboh...The importance of pyrimidines lies in the fact that they are structural components of a broad spectrum of key molecules that participate in diverse cellular functions, such as synthesis of DNA, RNA, lipids, and carbohydrates. Pyrimidine metabolism encompasses all enzymes involved in the synthesis, degradation, salvage, interconversion and transport of these molecules. In this review, we summarize recent publications that document how pyrimidine metabolism changes under a variety of conditions, including, when possible, those studies based on techniques of genomics, transcriptomics, proteomics, and metabolomics. First, we briefly look at the dynamics of pyrimidine metabolism during nonpathogenic cellular events. We then focus on changes that pathogen infections cause in the pyrimidine metabolism of their host. Next, we discuss the effects of antimetabolites and inhibitors, and finally we consider the consequences of genetic ma- nipulations, such as knock-downs, knock-outs, and knock-ins, of pyrimidine enzymes on pyrimidine metabolism in the cell.展开更多
A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The struc...A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The structures of the final compounds were confirmed by 1R, NMR, El-MS, elemental analysis, and X-ray diffraction. Preliminary bioassay results showed that some of the analogs exhibit excellent antitumor activity against MCF-7 and HepG2, especially compounds 3a, 3b, 3e and 3h exhibited higher activity than the positive control gefitinib.展开更多
A series of novel fluorinated thieno[2,3-d]pyrimidine derivatives incorporating 1,3,4-thiadiazole were synthesized by a facile microwave-assisted procedure,including the cyclization of 2-aminothiophene-3-carbonitrile ...A series of novel fluorinated thieno[2,3-d]pyrimidine derivatives incorporating 1,3,4-thiadiazole were synthesized by a facile microwave-assisted procedure,including the cyclization of 2-aminothiophene-3-carbonitrile with trifluoroacetic acid,chlorination and nucleophilic substitution reaction.This protocol offered such advantages as mild reaction conditions,short reaction time, simple puritication and good yields.The structures of the products were characterized by ~1H NMR,MS,elemental analysis and Xray diffraction.展开更多
A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with ...A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.展开更多
A facile microwave-assisted procedure for synthesis of novel fluorinated pyrazolo[3,4-d]pyrimidine derivatives containing 1,3,4-thiadiazole is described. This protocol presented such advantages as short reaction time,...A facile microwave-assisted procedure for synthesis of novel fluorinated pyrazolo[3,4-d]pyrimidine derivatives containing 1,3,4-thiadiazole is described. This protocol presented such advantages as short reaction time, high yields, simple purification and environmentally benign procedures. Their antitumor activities were evaluated against HL-60 by an MTT assay. The preliminary results indicated that some title compounds exhibit more potent antitumor inhibitory activity than doxorubicin （DOX）.展开更多
It is timely to consider the many facets of the small molecule orotic acid （OA）, which is well-known as an essential intermediate of pyrimidine de novo synthesis. In addition, it can be taken up by erythrocytes and ...It is timely to consider the many facets of the small molecule orotic acid （OA）, which is well-known as an essential intermediate of pyrimidine de novo synthesis. In addition, it can be taken up by erythrocytes and hepatocytes for conversion into uridine and for use in the pyrimidine recycling pathway. We discuss the link between dietary orotate and fatty liver in rats, and the potential for the alleviation of neonatal hyperbilirubinaemia. We address the development of orotate derivatives for application as anti-pyrimidine drugs, and of com- plexes with metal ions and organic cations to assist therapies of metabolic syndromes. Recent genetic data link human Miller syndrome to defects in the dihydroorotate dehydrogenase （DHODH） gene, hence to depleted orotate production. Another defect in pyrimidine biosynthesis, the orotic aciduria arising in humans and cattle with a deficiency of UMP synthase （UMPS）, has different symptoms. More recent work leads us to conclude that OA may have a role in regulating gene transcription.展开更多
A novel tandem reductive amination/intermolecular nucleophilic aromatic substitution (SNAr) sequence has been established for the synthesis of amine containing pyrimidine in formation of one carbon-oxygen and one carb...A novel tandem reductive amination/intermolecular nucleophilic aromatic substitution (SNAr) sequence has been established for the synthesis of amine containing pyrimidine in formation of one carbon-oxygen and one carbon-nitrogen bonds in a one-pot fashion. Treatment of aldehyde with arylamine, 2-methanesulfonyl-4,6-dimeth-oxypyrimidine and sodium borohydride provides good overall yield. The p-toluenesulfonic acid (PTSA) can be used as activator and is generally needed in the reaction. Dioxane is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF), MeCN, toluene and dichloromethane. The procedure is carried out effectively in the presence of K2CO3. The reaction proceeds smoothly with aromatic aldehydes and arylamines possessing elec-tron-donating or-withdrawing groups. This method can be applied to the synthesis of the oilseed rape herbicide and is superior to the classical one in several aspects: cutting out several purification steps, minimizing solvent use and chemical waste, and saving time. Its advantages such as operational convenience, high-efficient synthesis, and starting material availability make it a desirable method for preparing amines with molecular diversity and biological activity.展开更多
A series of imidazo[1,2-a]pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests sugges...A series of imidazo[1,2-a]pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.展开更多
基金supported by the National Natural Science Foundation of China(82104207)Natural Science Foundation of Zhejiang Province(LQ22H280001)。
文摘Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.
基金supported by the National Natural Science Foundation of China(32102283 to Mingming Yang)the Science and Technology Major Project of China National Tobacco Corporation(110202101056(LS-16))the Science and Technology Project of Shaanxi Branch of China National Tobacco Corporation(KJ-2021-02 and KJ-2022-04).
文摘Bacterial species of the genus Lysobacter are environmentally ubiquitous with strong antifungal biocontrol potential.Heat-stable antifungal factor(HSAF)secreted by the biocontrol bacterium Lysobacter enzymogenes OH11 has broad-spectrum and highly efficient antifungal activity.Studying the biosynthetic regulations of HSAF would lay an important foundation for strain engineering toward improved HSAF production.In this work,we demonstrate that Le0752,an orotidine-5´-phosphate decarboxylase enzyme(ODCase)catalyzing a pivotal step of the UMP de novo biosynthesis pathway,is vital for HSAF-mediated antimicrobial activities and growth of L.enzymogenes OH11,but not for twitching motility.This gene regulates the production of HSAF by affecting the expression of lafB,a key gene in the HSAF biosynthesis operon,through the transcription factor Clp.Interestingly,bioinformatics analysis revealed that Le0752 belongs to the Group III ODCases,whereas its homologs in the closely related genera Xanthomonas and Stenotrophomonas belong to Group I,which contains most ODCases from Gram-positive bacteria,Gram-negative bacteria and cyanobacteria.Moreover,the Group I ODCase PXO_3614 from the Xanthomonas oryzae pv.oryzae PXO99A strain complemented the Le0752 mutant in regulating HSAF-mediated antagonistic activity.Together,these results highlight the important requirement of de novo pyrimidine biosynthetic enzymes for antibiotic HSAF production in L.enzymogenes,which lays an important foundation for improving HSAF production via metabolic flow design and for dissecting the regulatory functions of bacterial ODCases.
基金supported by the National Natural Science Foundation of China(Nos.22077099,22171223 and 22307102)the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32)+5 种基金the Technology Innovation Leading Program of Shaanxi(Nos.2023KXJ-209 and 2024QCY-KXJ-142)the Key Research and Development Program of Shaanxi(No.2024GHZDXM-22)the Natural Science Basic Research Program of Shaanxi(Nos.2023-JC-YB-141 and 2022JQ-151)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080)the Yan’an City Science and Technology Project(No.2022SLZDCY-002)。
文摘Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.
文摘A formal[3+3]annulation of 3-aminopyrazoles with cinnamaldehydes or cinnamyl alcohols mediated by NH_(4)SCN has been developed.This protocol provides a practical route to construct 5-arylated pyrazolo[1,5-a]pyrimidines with high functional group tolerance.The use of NH_(4)SCN as the cyanide anion surrogate allows the transient generation of cyanohydrin,which shifts the reactive center within cinnamaldehydes from formyl group to alkene group to realize an opposite regiocontrol comparing with previous reports.
文摘Five rice ( Oryza sativa L.) cultivars, widely planted in South China, were grown in greenhouse with or without supplemental UV_B radiation at level of 13.6 kJ·m -2 ·d -1 . After 15 day_UV_B treatment, significant intraspecific differences were observed in plant height, photosynthetic rate and total biomass. Based on the total biomass accumulation, cultivar “Tesanai” was found to be the most sensitive, and cultivar “Luhuangzhan” was the most tolerant species to UV_B radiation. UV_B induced cyclobutane pyrimidine dimer (CPD) in rice DNA were quantified by ELISA with specific monoclonal antibody. CPD accumulations in DNA extracted from 5 rice cultivars were remarkably increased by UV_B radiation, and it was confirmed that there was a strong positive correlation between CPD accumulation and the inhibition of total biomass. Photorepair was proved to be the predominant mode of CPD repair in UV_B irradiated rice. Light_dependent removal of CPD was very fast as compared with dark repair. Different levels of CPD accumulation among rice cultivars were related with different capacity of CPD photorepair. Capacity of light_dependent CPD removal may play an important role in UV_B resistance of rice.
文摘Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotschibabin reaction of a-bromoacetophenones with 2-aminopyrimidine in good yields.
文摘?-(2-methylthio -4 -methyl -5 -pyrimidinyl)-2. 4 - pentadiyn- 1 -ol- (4- N. N-dimethylamino-azobenzene -4' -sulfonate) (PDABS - 1 ). ②5 -(2 -methylthio -4 -methyl -5-pyrimidinyl)- 2.4 -pentadiyn- 1 -ol - (azobenzene - 4 -sulfonate) (PDABS -2 ). ③2. 4 -hexadiyn - 1 -ol-6- (4 - N, N-dimethylamino-azobenzene-4'-sulfonate) (HDABS - 1 ), ④2. 4 -hexadiyn - 1-ol -6 - (azobenzene4-sulfonate) (HDABS-2), the four new compounds are synthesize. The structures of the new compounds have been demonstrdted by elemental analysis. IR(KBr). 1H-NMR (CD3CO/TMS),MS. Their X(3), d33. βμ and the fabrication of their polarization orientated thin film also have ben reported in this paper.
文摘Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.
基金This work was supported by the Academy Technology Development Foundation of Shanghai (2000D07)
文摘The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of the target compound, we report its crystal structure and herbi- cidal behavior in the present paper. Crystallographic data: C15H12N4O4Cl2S, Mr = 415.25, mono- clinic, space group P21/n, a = 10.7361(8), b = 11.9610(9), c = 13.0990(10) ?, β = 96.988(2)o, Z = 4, V = 1669.6(2) ?3, Dc = 1.652 g/cm3, F(000) = 848, R = 0.0394, wR = 0.0797 and μ(MoKα) = 0.545 mm-1.
文摘The title compound 5,7-dimethoxy-(2,4-dichlorophenoxyacetylimino)-2H-1,2,4- thiadiazolo[2,3-a]pyrimidine has been synthesized. In order to investigate the relationship between the structure and herbicidal activity of the target compound, we report its crystal structure and herbi- cidal behavior in the present paper. Crystallographic data: C15H12N4O4Cl2S, Mr = 415.25, mono- clinic, space group P21/n, a = 10.7361(8), b = 11.9610(9), c = 13.0990(10) ?, β = 96.988(2)o, Z = 4, V = 1669.6(2) ?3, Dc = 1.652 g/cm3, F(000) = 848, R = 0.0394, wR = 0.0797 and μ(MoKα) = 0.545 mm-1.
文摘2-Aminocyclopenta[d]pyrimidines 3a-c were achieved via a one-pot, three-component reactions of cyclopentanone 1, aromatic aldehyde and guanidine hydrochloride （1：2：1 molar ratio）. Also, cyclization of 2,5-bis-（arylmethylidene）cyclopentanones 2 with guanidine hydrochloride （1：1 molar ratio） in methanol in the presence of sodium methoxide afforded cyclopenta-[d]pyrimidines 3. Compound 3c has been shown to be a useful building block for the synthesis of some novel pyrimido[ 1,2-a]pyrimidines 5, 7 and 12. The structures of the newly synthesized compounds were confirmed on the basis of analytical and spectral data,
文摘Four novel pyridimine compounds were prepared. The yield of the intermediates was improved with new method making use of Pd(Ⅱ) catalyst and cuprous acetylide which were proved to be practital in the formation of the acetylide which were proved to be practical in the formation of the acetylides. Their nonlinear optical properties were briefly studied.
基金supported in part by the Universidad de los Andes Faculty of Sciencesby basic sciences project P13.700022.007 from the University of los Andes Office of Research+1 种基金by COLCIENCIAS grant # 120-4521-28532Colciencias (Programa de Apoyo a Doctorados Nacionales) for the financial support of the Ph.D. studies of M.F.G. and H.Y.N.-O
文摘The importance of pyrimidines lies in the fact that they are structural components of a broad spectrum of key molecules that participate in diverse cellular functions, such as synthesis of DNA, RNA, lipids, and carbohydrates. Pyrimidine metabolism encompasses all enzymes involved in the synthesis, degradation, salvage, interconversion and transport of these molecules. In this review, we summarize recent publications that document how pyrimidine metabolism changes under a variety of conditions, including, when possible, those studies based on techniques of genomics, transcriptomics, proteomics, and metabolomics. First, we briefly look at the dynamics of pyrimidine metabolism during nonpathogenic cellular events. We then focus on changes that pathogen infections cause in the pyrimidine metabolism of their host. Next, we discuss the effects of antimetabolites and inhibitors, and finally we consider the consequences of genetic ma- nipulations, such as knock-downs, knock-outs, and knock-ins, of pyrimidine enzymes on pyrimidine metabolism in the cell.
基金financially supported by the National Natural Science Foundation of China(No.21262012)the Open Fund of Key Laboratory of Biologic Resources Protection and Utilization of Hubei Province(No.PKLHB1314)
文摘A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The structures of the final compounds were confirmed by 1R, NMR, El-MS, elemental analysis, and X-ray diffraction. Preliminary bioassay results showed that some of the analogs exhibit excellent antitumor activity against MCF-7 and HepG2, especially compounds 3a, 3b, 3e and 3h exhibited higher activity than the positive control gefitinib.
基金the Natural Science Foundation of Hubei Province(No2011CDB087)Scientific Research Fund of Hubei Provincial Education Department(NoD20111904)Open Fund of Key Laboratory of Biological Resources Protection and Utilization of Hubei Province(NoPKLHB1102)for generous financial support
文摘A series of novel fluorinated thieno[2,3-d]pyrimidine derivatives incorporating 1,3,4-thiadiazole were synthesized by a facile microwave-assisted procedure,including the cyclization of 2-aminothiophene-3-carbonitrile with trifluoroacetic acid,chlorination and nucleophilic substitution reaction.This protocol offered such advantages as mild reaction conditions,short reaction time, simple puritication and good yields.The structures of the products were characterized by ~1H NMR,MS,elemental analysis and Xray diffraction.
基金receiving a fellowship from UGCNew Delhi[University Grant Commission,the XIth plan(Faculty Improvement Programme)]DST and UGC for providing funds to the department under FIST and SAP programme
文摘A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.
基金the National Nature Science Foundation of Hubei Province(No.2008CDB016)the Scientific Research Fund of Hubei Provincial Education Department(No.D20111904)
文摘A facile microwave-assisted procedure for synthesis of novel fluorinated pyrazolo[3,4-d]pyrimidine derivatives containing 1,3,4-thiadiazole is described. This protocol presented such advantages as short reaction time, high yields, simple purification and environmentally benign procedures. Their antitumor activities were evaluated against HL-60 by an MTT assay. The preliminary results indicated that some title compounds exhibit more potent antitumor inhibitory activity than doxorubicin （DOX）.
文摘It is timely to consider the many facets of the small molecule orotic acid （OA）, which is well-known as an essential intermediate of pyrimidine de novo synthesis. In addition, it can be taken up by erythrocytes and hepatocytes for conversion into uridine and for use in the pyrimidine recycling pathway. We discuss the link between dietary orotate and fatty liver in rats, and the potential for the alleviation of neonatal hyperbilirubinaemia. We address the development of orotate derivatives for application as anti-pyrimidine drugs, and of com- plexes with metal ions and organic cations to assist therapies of metabolic syndromes. Recent genetic data link human Miller syndrome to defects in the dihydroorotate dehydrogenase （DHODH） gene, hence to depleted orotate production. Another defect in pyrimidine biosynthesis, the orotic aciduria arising in humans and cattle with a deficiency of UMP synthase （UMPS）, has different symptoms. More recent work leads us to conclude that OA may have a role in regulating gene transcription.
基金Project (Nos. Y407118 and D3080282) supported by the Natural Science Foundation of Zhejiang Province, China
文摘A novel tandem reductive amination/intermolecular nucleophilic aromatic substitution (SNAr) sequence has been established for the synthesis of amine containing pyrimidine in formation of one carbon-oxygen and one carbon-nitrogen bonds in a one-pot fashion. Treatment of aldehyde with arylamine, 2-methanesulfonyl-4,6-dimeth-oxypyrimidine and sodium borohydride provides good overall yield. The p-toluenesulfonic acid (PTSA) can be used as activator and is generally needed in the reaction. Dioxane is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF), MeCN, toluene and dichloromethane. The procedure is carried out effectively in the presence of K2CO3. The reaction proceeds smoothly with aromatic aldehydes and arylamines possessing elec-tron-donating or-withdrawing groups. This method can be applied to the synthesis of the oilseed rape herbicide and is superior to the classical one in several aspects: cutting out several purification steps, minimizing solvent use and chemical waste, and saving time. Its advantages such as operational convenience, high-efficient synthesis, and starting material availability make it a desirable method for preparing amines with molecular diversity and biological activity.
基金This research was supported by the National Natural Science Foundation of China （No.30472083）.
文摘A series of imidazo[1,2-a]pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.
