The Pfitzinger reaction has long served as a notable synthesis pathway for quinoline-4-carboxylic acids.Although recognized for its synthetic potential since its discovery>138 years ago,a truly catalytic variant ha...The Pfitzinger reaction has long served as a notable synthesis pathway for quinoline-4-carboxylic acids.Although recognized for its synthetic potential since its discovery>138 years ago,a truly catalytic variant has remained elusive until now.Herein,we present a novel 2-tert-butyl-1,1,3,3-tetramethylguanidine(BTMG)-catalyzed Pfitzinger reaction that employs N-[(α-trifluoromethyl)vinyl]isatins with amines and alcohols,providing direct routes to 2-CF_(3)-quinoline-4-carboxamides and carboxylic esters.This method is not only green and environmentally benign but also accommodates the introduction of other functional groups like CF_(2)H and CO_(2)Me at the C2 position of quinoline skeleton.The utility of this methodology was demonstrated by the broad substrate scope,the late-stage modification of commercial drugs,and the diverse derivatization of quinoline framework.More importantly,this work not only opens up a new avenue for the activation of amide C-N bonds in catalytic reaction development,but also unlocks the huge potential of some 2-trifluoromethyl quinolines with strong inhibitory activity against PTP1B or optoelectronic application in organic light-emitting diodes.展开更多
The asymmetric addition of aromatic organometallic compounds to the carbonyl group(C-3)of isatins,catalyzed by transition metals,has emerged as a remarkably efficient method for the synthesis of chiral 3-hydroxyoxindo...The asymmetric addition of aromatic organometallic compounds to the carbonyl group(C-3)of isatins,catalyzed by transition metals,has emerged as a remarkably efficient method for the synthesis of chiral 3-hydroxyoxindoles.Here,an exceptionally enantioselective approach was developed for the first time to achieve a catalytic NHK reaction of isatins with aromatic halides(both aryl and heteroaryl).Utilizing chiral cobalt complexes as catalysts,and the presence of a diboron reagent B_(2)nep_(2)as both a reducing agent and determinant in enantiocontrol,has resulted in the triumphantly achieved synthesis of enantioenriched products.Compared to reported strategies,this approach exhibits remarkable compatibility with substrates bearing sensitive functional groups,such as halides and borate esters,while also eliminating the need for organometallic reagents as required in previous strategies.Through experimental investigations,the presence of aryl-cobalt species during the addition process was confirmed,rather than in-situ generation of an arylboron reagent.Furthermore,the successful attainment of the R absolute configuration through aryl addition was demonstrated.展开更多
The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones(27 examples,up to 98% yield) from readily available indoles and isatin derivatives are d...The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones(27 examples,up to 98% yield) from readily available indoles and isatin derivatives are described.This protocol shows well tolerance of different functional groups and features mild reaction conditions such as short reaction time(~1 h),no usage of catalyst,easy operation and product isolation.Of particular intere st is the formation of two C-C bonds and one all-carbon quaternary center.This protocol could serve as an alternative strategy to synthesize biologically important 3,3-di(indolyl)indolin-2-ones for biological testing.展开更多
Described here is the first example of Cu(0)-catalyzed intramolecular decarbonylative rearrangements of readily available N-aryl isatins assisted by solvent dimethyl sulfoxide(DMSO)under air atmosphere and additive-fr...Described here is the first example of Cu(0)-catalyzed intramolecular decarbonylative rearrangements of readily available N-aryl isatins assisted by solvent dimethyl sulfoxide(DMSO)under air atmosphere and additive-free conditions leading to various biologically important acridones in good to excellent yields.This novel transformation is proposed to go through a sequential DMSO-aided Cu insertion into the amide C-N bond,CO extrusion,Cu migration,reductive elimination and DMSO-aided proton migration processes,involving multiple types of bond cleavage and formation in a single chemical step.展开更多
Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using...Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds（11a-13c） which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa（MIC = 6.25 μg/m L）.Analysis of the structure-activity relationship showed that the incorporation of（thio）urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a-12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins（13a-13c） still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases（compounds 1a-1d） in our future studies.展开更多
A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed, The reaction features the mild reaction conditions, broad su...A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed, The reaction features the mild reaction conditions, broad substrate scope, metal-free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate the antimicrobial activities towards two Gram-negative bacterial strains （Escherichia coli, and Klebsiella pneumonia） and two Gram-positive bacterial strains （Staphylococcus epidermidis, and Staphylococcus aureus） using the Broth microdilution method.展开更多
The first cyclization/decarboxylation reaction of isatins with acyl chlorides promoted by 4-dimethylaminopyridine(DMAP)was described and a series of desired 3-alkenyl-oxindoles were obtained in good yields(up to 80%)a...The first cyclization/decarboxylation reaction of isatins with acyl chlorides promoted by 4-dimethylaminopyridine(DMAP)was described and a series of desired 3-alkenyl-oxindoles were obtained in good yields(up to 80%)and E/Z selectivities(up to 6.4/1).This protocol provided a new and feasible access to 3-alkenyl-oxindoles.展开更多
The development of alkaline fuel cells is moving forward at an accelerated pace,and the application of ether-free bonded polymers to anion exchange membranes(AEMs)has been widely investigated.However,the question of ...The development of alkaline fuel cells is moving forward at an accelerated pace,and the application of ether-free bonded polymers to anion exchange membranes(AEMs)has been widely investigated.However,the question of the“trade-off”between AEM ionic conductivity and dimensional stability remains difficult.The strategy of inducing microphase separation to improve the performance of AEM has attracted much attention recently,but the design of optimal molecular structures is still being explored.Here,this work introduced different ratios of 3-bromo-1,1,1-trifluoroacetone(x=40,50,and 60)into the main chain of poly(p-terphenylene isatin).Because fluorinated groups have excellent hydrophobicity,hydrophilic hydroxyl-containing side chains are introduced to jointly adjust the formation of phase separation structure.The results show that PTI-PTF_(50)-NOH AEM with the appropriate fluorinated group ratio has the best ionic conductivity and alkali stability under the combined effect of both.It has an ionic conductivity of 133.83 mS cm^(-1)at 80°C.In addition,the OH-conductivity remains at 89%of the initial value at 80°C and 3 M KOH for 1056 h of immersion.The cell polarization curve based on PTI-PTF_(50)-NOH shows a power density of 734.76 mW cm^(-2)at a current density of 1807.7 mA cm^(-2).展开更多
The c-Jun N-terminal kinase （JNK） is involved in a variety of important cellular processes and aberrant JNK activity is associated with many human diseases.The ligand-based and receptor-based alignment rules were us...The c-Jun N-terminal kinase （JNK） is involved in a variety of important cellular processes and aberrant JNK activity is associated with many human diseases.The ligand-based and receptor-based alignment rules were used to build 3D-QSAR models for a series of N-benzyl isatin oximes JNK inhibitors. The best models were obtained for the receptor-based alignment with CoMSIA combining steric （S）, electrostatic （E）, and hydrogen bond donor （D） and hydrogen bond acceptor （A） fields （q2 = 0.759, r2 = 0.966, r2 pred = 0.703）. Based on the contour maps of RB CoMSIA model, some key structural factors responsible for inhibitory activity were investigated. Large groups at N-substituent or R6 position are preferred to interact with hydrophobic residues Ile70, Asp150, Ala151, Asn152 and Ser193. Electron-donating or hydrogen bond donor groups on the isatin ring would form polar and hydrogen bond with the negative-charged residue Glu147. In addition, electron-withdrawing groups or hydrogen bond acceptor group near the N-substituent would enhance inhibitory activity. The results are in good accordance and complementary to each other. The developed models could provide guidance in the rational design of more potent and selective JNK inhibitors.展开更多
New dibutyltin(IV) complexes of Schiff base derived from 5-chloroindoline-2,3-dione, indoline- 2,3-dione with amino acids (tryptophan, alanine and valine) were synthesized and characterized by elemental analysis, IR, ...New dibutyltin(IV) complexes of Schiff base derived from 5-chloroindoline-2,3-dione, indoline- 2,3-dione with amino acids (tryptophan, alanine and valine) were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, and biological activity. The analytical data showed that the Schiff base ligand acts as bidentate towards metal ions via the azomethine nitrogen and carboxylate oxygen by a stoichiometric reaction of M:L (1:2) to form metal complexes. NMR (1H, 13C and 119Sn) spectral data of the ligands and metal complex agree with proposed structures. The conductivity values between 14 - 27 ohm-1cm2mol-1 in DMF imply the presence of non-electrolyte species. 3D molecular modeling and analysis of bond lengths and bond angles have also been conducted for a representative compound, [Bu2Sn(L2)2], to substantiate the proposed structures. Antibacterial results indicate that the metal complexes are more active than the free ligands.展开更多
The effects of isatin (2,3-dioxo-indole) and isatin analogues (5-methylisatin, 6-hydroxyisatin, 7-ethylisatin, N-acety- lisatin) were tested on prostaglandin E2 (PGE2)-induced fever in mice and rats. Two modes of admi...The effects of isatin (2,3-dioxo-indole) and isatin analogues (5-methylisatin, 6-hydroxyisatin, 7-ethylisatin, N-acety- lisatin) were tested on prostaglandin E2 (PGE2)-induced fever in mice and rats. Two modes of administration were tested. Isatin or an analogue was injected simultaneously with PGE2 and the development of fever was tested, or the test compound was given 30 min following PGE2 administration and the effects on the already existing fever were measured, in mice and in rats. Isatin in a dose of 3.12 mg/kg ip was found to block the development of PGE2-induced fever in mice, while in a dose of 12.5 mg/kg ip it attenuated the existing fever. In rats isatin in a dose of 12.5 mg/kg ip blocked fever initiation, and at 25.0 mg/kg ip attenuated existing PGE2-induced fever. In mice, 5-methylisatin in a dose of 0.21 mg/kg ip blocked the initiation of fever, and at 6.72 mg/kg ip attenuated the existing fever. In rats in a dose of 3.36 mg/kg ip it blocked the development of fever, and at 13.44 mg/kg ip attenuated existing PGE2-induced fever. In mice 5,6-dimetylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and attenuated the existing fever in mice, in rats in a dose of 0.42 mg/kg ip it blocked the initiation of fever, and at 0.21 mg/kg ip attenuated the existing PGE2-induced fever. In mice 6-hydroxyisatin in a dose of 5.2 mg/kg blocked the development of fever, and at 10.4 mg/kg attenuated the existing fever. In rats in a dose of 10.40 mg/kg ip it blocked fever development and also attenuated the existing fever. In mice, 7-ethylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and also attenuated the existing fever. In rats, a dose of 0.11 mg/kg both blocked fever initiation and also attenuated the existing fever. In mice, N-acethylisatin in the dose of 0.005 mg/kg blocked fever initiation, while at 1.024 mg/kg it attenuated existing fever, in rats, in a dose of 0.096 mg/kg it blocked fever initiation, and at 0.384 mg/kg attenuated the existing fever. The results demonstrate that 7-ethyl- and N-acetylisatin are the most effective of these compounds both in blocking the development of PGE2-induced fever and also in attenuating existing the PGE 2-induced fever.展开更多
A series of 5-substitued-3-（5-（4-（furan-2-yl）-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-thiadiazol-2- ylimino）indolin-2-one derivatives were synthesized,characterized and were screened for an...A series of 5-substitued-3-（5-（4-（furan-2-yl）-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-thiadiazol-2- ylimino）indolin-2-one derivatives were synthesized,characterized and were screened for anti-bacterial,anti-fungal and antitubercular activity.展开更多
A series of new methyl-4-（（substituted phenyl）[6H-indolo（2,3-b）quinoxalin-6yl]methylamino）benzoate derivatives have been synthesized and assayed for their antibacterial activity on 9 different bacterial strains....A series of new methyl-4-（（substituted phenyl）[6H-indolo（2,3-b）quinoxalin-6yl]methylamino）benzoate derivatives have been synthesized and assayed for their antibacterial activity on 9 different bacterial strains.Among the screened compounds 2e-2g exhibited potent inhibitory activity compared to standard drug employed,worth further investigation.展开更多
A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as wel...A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as well as cytotoxicity. All benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids exhibited considerable in vitro anti-mycobacterial activities against the tested three MTB strains, and all of them also showed acceptable cytotoxicity. The most active hybrid 7f was >4.8 and >51 folds more potent than the first line anti-TB agents RIF and INH against both drug-sensitive MTB H_(37)Rv and MDR-TB isolates, respectively. The results demonstrated the potential utility of benzofuran-isatin-hydroxylimine/-thiosemicarbazide hybrids as anti-TB agents.展开更多
A new series of isatin semicarbazide derivatives（7a-7j） were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick techn...A new series of isatin semicarbazide derivatives（7a-7j） were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively.The ulcerogenicity was also determined for all the compounds.Some of the compounds showed moderate enhancement of the activity.Among the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.展开更多
Tuberculosis（TB） is one of the most common and even fatal infectious diseases known to mankind.Millions of new cases are reported every year over the world,and one-third of the world＇s population is potentially inf...Tuberculosis（TB） is one of the most common and even fatal infectious diseases known to mankind.Millions of new cases are reported every year over the world,and one-third of the world＇s population is potentially infected with mycobacteria tuberculosis（MTB）.Research to develop novel anti-TB drugs led to the identification of several isatin-based antimycobacterial agents,among which a number of potential candidates displayed excellent antimycobacterial activity and were found to be free of cytotoxicity.This review outlines the advances in the application of isatin hybrids as antimycobacterial agents and the critical aspects of design and structure-activity relationship of these derivatives.展开更多
A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and...A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. smegmatis CMCC 93202. Compounds 3a―3f, 5a, 5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis（MTB） H37Rv ATCC 27294 and MDR-MTB 09710. All the target com pounds[minimum inhibitory concentration（MIC）： 0.39―〉16 μg/mL] were far more active than rifampin（MIC： 2.0―〉256 μg/mL）, but less active than moxifloxacin（MIC： 0.1―1.0 μg/mL） against the three tested strains. The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M. smegmatis CMCC 93202, 2 fold more potent than rifampin against MTB H37Rv ATCC 27294, and 16―〉64 fold more potent than ethambutol, isoniazid and rifampin against MDR-MTB 09710.展开更多
The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C5...The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine （MPTP） Bax protein expression was significantly reduced in isatin （100, 200 mg/kg）-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.展开更多
The functionalized spiro[indoline-3,40-pyrano[3,2-h]quinolines] were efficiently prepared in high yields from three-component reaction of 8-hydroxyquinoline, isatins and malononitrile or ethyl cyanoacetate in ethanol ...The functionalized spiro[indoline-3,40-pyrano[3,2-h]quinolines] were efficiently prepared in high yields from three-component reaction of 8-hydroxyquinoline, isatins and malononitrile or ethyl cyanoacetate in ethanol at room temperature for about 12 h in the presence of piperidine.展开更多
An efficient asymmetric alkenylation between 3-vinylindoles and isatin derivatives was developed under catalysis of a chiral copper complex.A series of optically active 3-alkenyl-3-substituted oxindoles were obtained ...An efficient asymmetric alkenylation between 3-vinylindoles and isatin derivatives was developed under catalysis of a chiral copper complex.A series of optically active 3-alkenyl-3-substituted oxindoles were obtained in excellent yields and stereoselectivities.The reaction mechanism was proposed and supported by DFT calculation.展开更多
基金National Natural Science Foundation of China(Nos.22171056,22122402,21801050)Outstanding Youth Project of Guangdong Natural Science Foundation(Nos.2024B1515020036,2021B1515020048)+3 种基金Guangdong Natural Science Foundation(Nos.2023A1515011313,2021A1515010510,2024A1515030037)Tertiary Education Scientific Research Project of Guangzhou Municipal Education Bureau(No.202235305)the Open Fund from Key Laboratory of Organofluorine ChemistryShanghai Engineering Research Center of Molecular Therapeutics and New Drug Development are gratefully acknowledged for financial support.
文摘The Pfitzinger reaction has long served as a notable synthesis pathway for quinoline-4-carboxylic acids.Although recognized for its synthetic potential since its discovery>138 years ago,a truly catalytic variant has remained elusive until now.Herein,we present a novel 2-tert-butyl-1,1,3,3-tetramethylguanidine(BTMG)-catalyzed Pfitzinger reaction that employs N-[(α-trifluoromethyl)vinyl]isatins with amines and alcohols,providing direct routes to 2-CF_(3)-quinoline-4-carboxamides and carboxylic esters.This method is not only green and environmentally benign but also accommodates the introduction of other functional groups like CF_(2)H and CO_(2)Me at the C2 position of quinoline skeleton.The utility of this methodology was demonstrated by the broad substrate scope,the late-stage modification of commercial drugs,and the diverse derivatization of quinoline framework.More importantly,this work not only opens up a new avenue for the activation of amide C-N bonds in catalytic reaction development,but also unlocks the huge potential of some 2-trifluoromethyl quinolines with strong inhibitory activity against PTP1B or optoelectronic application in organic light-emitting diodes.
基金the National Key R&D Program of China(No.2022YFA1503200)the National Natural Science Foundation of China(Nos.22025104,22171134,and 21972064)the Fundamental Research Funds for the Central Universities(No.020514380254)is greatly appreciated.
文摘The asymmetric addition of aromatic organometallic compounds to the carbonyl group(C-3)of isatins,catalyzed by transition metals,has emerged as a remarkably efficient method for the synthesis of chiral 3-hydroxyoxindoles.Here,an exceptionally enantioselective approach was developed for the first time to achieve a catalytic NHK reaction of isatins with aromatic halides(both aryl and heteroaryl).Utilizing chiral cobalt complexes as catalysts,and the presence of a diboron reagent B_(2)nep_(2)as both a reducing agent and determinant in enantiocontrol,has resulted in the triumphantly achieved synthesis of enantioenriched products.Compared to reported strategies,this approach exhibits remarkable compatibility with substrates bearing sensitive functional groups,such as halides and borate esters,while also eliminating the need for organometallic reagents as required in previous strategies.Through experimental investigations,the presence of aryl-cobalt species during the addition process was confirmed,rather than in-situ generation of an arylboron reagent.Furthermore,the successful attainment of the R absolute configuration through aryl addition was demonstrated.
基金supported by the National Natural Science Foundation of China(Nos.81773562,81703326 and 81973177)The Open Project of State Key Laboratory of Natural Medicines(No.SKLNMKF202005)China Postdoctoral Science Foundation(Nos.2018M630840 and 2019T120641)。
文摘The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones(27 examples,up to 98% yield) from readily available indoles and isatin derivatives are described.This protocol shows well tolerance of different functional groups and features mild reaction conditions such as short reaction time(~1 h),no usage of catalyst,easy operation and product isolation.Of particular intere st is the formation of two C-C bonds and one all-carbon quaternary center.This protocol could serve as an alternative strategy to synthesize biologically important 3,3-di(indolyl)indolin-2-ones for biological testing.
基金National Natural Science Foundation of China(Nos.U1604285 and 21877206)the Program for Changjiang Scholars and Innovative Research Team in University of China(No.IRT1061)the 111 Project(No.D17007)。
文摘Described here is the first example of Cu(0)-catalyzed intramolecular decarbonylative rearrangements of readily available N-aryl isatins assisted by solvent dimethyl sulfoxide(DMSO)under air atmosphere and additive-free conditions leading to various biologically important acridones in good to excellent yields.This novel transformation is proposed to go through a sequential DMSO-aided Cu insertion into the amide C-N bond,CO extrusion,Cu migration,reductive elimination and DMSO-aided proton migration processes,involving multiple types of bond cleavage and formation in a single chemical step.
文摘Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds（11a-13c） which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa（MIC = 6.25 μg/m L）.Analysis of the structure-activity relationship showed that the incorporation of（thio）urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a-12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins（13a-13c） still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases（compounds 1a-1d） in our future studies.
基金Supporting information for this article is available on the WWW under http：//dx.doi.org/10.1002/cjoc,201700280 or from the author.Acknowledgement The work was partially supported by the National Natural Science Foundation of China （No. 21172001, 21372008）, the Natural Science Foundation of Education Administration of Anhui Province （KJ2016A267）, the Special and Excellent Research Fund of Anhui Normal University and the Doctoral Scientific Research Foundation of Anhui Normal University （No. 2016XJJ110）.
文摘A green and highly efficient synthetic method for the synthesis of quinazoline-2,4-diones with hydrogen peroxide as the terminal oxidant has been developed, The reaction features the mild reaction conditions, broad substrate scope, metal-free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate the antimicrobial activities towards two Gram-negative bacterial strains （Escherichia coli, and Klebsiella pneumonia） and two Gram-positive bacterial strains （Staphylococcus epidermidis, and Staphylococcus aureus） using the Broth microdilution method.
基金We are grateful for the grants from the National Natural Science Foundation of China(No.21272230)Western Light Talent Culture Project of Chinese Academy of Sciences.
文摘The first cyclization/decarboxylation reaction of isatins with acyl chlorides promoted by 4-dimethylaminopyridine(DMAP)was described and a series of desired 3-alkenyl-oxindoles were obtained in good yields(up to 80%)and E/Z selectivities(up to 6.4/1).This protocol provided a new and feasible access to 3-alkenyl-oxindoles.
基金Natural Science Foundation of China(grant nos 22075031)Jilin Provincial Science&Technology Department(grant nos 20220201105GX)Jilin Provincial Development and Reform Commission(grant nos 2023C034-4)。
文摘The development of alkaline fuel cells is moving forward at an accelerated pace,and the application of ether-free bonded polymers to anion exchange membranes(AEMs)has been widely investigated.However,the question of the“trade-off”between AEM ionic conductivity and dimensional stability remains difficult.The strategy of inducing microphase separation to improve the performance of AEM has attracted much attention recently,but the design of optimal molecular structures is still being explored.Here,this work introduced different ratios of 3-bromo-1,1,1-trifluoroacetone(x=40,50,and 60)into the main chain of poly(p-terphenylene isatin).Because fluorinated groups have excellent hydrophobicity,hydrophilic hydroxyl-containing side chains are introduced to jointly adjust the formation of phase separation structure.The results show that PTI-PTF_(50)-NOH AEM with the appropriate fluorinated group ratio has the best ionic conductivity and alkali stability under the combined effect of both.It has an ionic conductivity of 133.83 mS cm^(-1)at 80°C.In addition,the OH-conductivity remains at 89%of the initial value at 80°C and 3 M KOH for 1056 h of immersion.The cell polarization curve based on PTI-PTF_(50)-NOH shows a power density of 734.76 mW cm^(-2)at a current density of 1807.7 mA cm^(-2).
基金supported by the Beijing Natural Science Foundation(Grant No.2123062)Research Fund for the Doctoral Program of Higher Education of China(Grant No.20121103120008)Science and Tech-nology Foundation of Beijing University of Technology(Grant No.ykj-2012-8725)
文摘The c-Jun N-terminal kinase （JNK） is involved in a variety of important cellular processes and aberrant JNK activity is associated with many human diseases.The ligand-based and receptor-based alignment rules were used to build 3D-QSAR models for a series of N-benzyl isatin oximes JNK inhibitors. The best models were obtained for the receptor-based alignment with CoMSIA combining steric （S）, electrostatic （E）, and hydrogen bond donor （D） and hydrogen bond acceptor （A） fields （q2 = 0.759, r2 = 0.966, r2 pred = 0.703）. Based on the contour maps of RB CoMSIA model, some key structural factors responsible for inhibitory activity were investigated. Large groups at N-substituent or R6 position are preferred to interact with hydrophobic residues Ile70, Asp150, Ala151, Asn152 and Ser193. Electron-donating or hydrogen bond donor groups on the isatin ring would form polar and hydrogen bond with the negative-charged residue Glu147. In addition, electron-withdrawing groups or hydrogen bond acceptor group near the N-substituent would enhance inhibitory activity. The results are in good accordance and complementary to each other. The developed models could provide guidance in the rational design of more potent and selective JNK inhibitors.
文摘New dibutyltin(IV) complexes of Schiff base derived from 5-chloroindoline-2,3-dione, indoline- 2,3-dione with amino acids (tryptophan, alanine and valine) were synthesized and characterized by elemental analysis, IR, electronic spectra, conductance measurements, and biological activity. The analytical data showed that the Schiff base ligand acts as bidentate towards metal ions via the azomethine nitrogen and carboxylate oxygen by a stoichiometric reaction of M:L (1:2) to form metal complexes. NMR (1H, 13C and 119Sn) spectral data of the ligands and metal complex agree with proposed structures. The conductivity values between 14 - 27 ohm-1cm2mol-1 in DMF imply the presence of non-electrolyte species. 3D molecular modeling and analysis of bond lengths and bond angles have also been conducted for a representative compound, [Bu2Sn(L2)2], to substantiate the proposed structures. Antibacterial results indicate that the metal complexes are more active than the free ligands.
文摘The effects of isatin (2,3-dioxo-indole) and isatin analogues (5-methylisatin, 6-hydroxyisatin, 7-ethylisatin, N-acety- lisatin) were tested on prostaglandin E2 (PGE2)-induced fever in mice and rats. Two modes of administration were tested. Isatin or an analogue was injected simultaneously with PGE2 and the development of fever was tested, or the test compound was given 30 min following PGE2 administration and the effects on the already existing fever were measured, in mice and in rats. Isatin in a dose of 3.12 mg/kg ip was found to block the development of PGE2-induced fever in mice, while in a dose of 12.5 mg/kg ip it attenuated the existing fever. In rats isatin in a dose of 12.5 mg/kg ip blocked fever initiation, and at 25.0 mg/kg ip attenuated existing PGE2-induced fever. In mice, 5-methylisatin in a dose of 0.21 mg/kg ip blocked the initiation of fever, and at 6.72 mg/kg ip attenuated the existing fever. In rats in a dose of 3.36 mg/kg ip it blocked the development of fever, and at 13.44 mg/kg ip attenuated existing PGE2-induced fever. In mice 5,6-dimetylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and attenuated the existing fever in mice, in rats in a dose of 0.42 mg/kg ip it blocked the initiation of fever, and at 0.21 mg/kg ip attenuated the existing PGE2-induced fever. In mice 6-hydroxyisatin in a dose of 5.2 mg/kg blocked the development of fever, and at 10.4 mg/kg attenuated the existing fever. In rats in a dose of 10.40 mg/kg ip it blocked fever development and also attenuated the existing fever. In mice, 7-ethylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and also attenuated the existing fever. In rats, a dose of 0.11 mg/kg both blocked fever initiation and also attenuated the existing fever. In mice, N-acethylisatin in the dose of 0.005 mg/kg blocked fever initiation, while at 1.024 mg/kg it attenuated existing fever, in rats, in a dose of 0.096 mg/kg it blocked fever initiation, and at 0.384 mg/kg attenuated the existing fever. The results demonstrate that 7-ethyl- and N-acetylisatin are the most effective of these compounds both in blocking the development of PGE2-induced fever and also in attenuating existing the PGE 2-induced fever.
文摘A series of 5-substitued-3-（5-（4-（furan-2-yl）-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-thiadiazol-2- ylimino）indolin-2-one derivatives were synthesized,characterized and were screened for anti-bacterial,anti-fungal and antitubercular activity.
文摘A series of new methyl-4-（（substituted phenyl）[6H-indolo（2,3-b）quinoxalin-6yl]methylamino）benzoate derivatives have been synthesized and assayed for their antibacterial activity on 9 different bacterial strains.Among the screened compounds 2e-2g exhibited potent inhibitory activity compared to standard drug employed,worth further investigation.
文摘A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as well as cytotoxicity. All benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids exhibited considerable in vitro anti-mycobacterial activities against the tested three MTB strains, and all of them also showed acceptable cytotoxicity. The most active hybrid 7f was >4.8 and >51 folds more potent than the first line anti-TB agents RIF and INH against both drug-sensitive MTB H_(37)Rv and MDR-TB isolates, respectively. The results demonstrated the potential utility of benzofuran-isatin-hydroxylimine/-thiosemicarbazide hybrids as anti-TB agents.
文摘A new series of isatin semicarbazide derivatives（7a-7j） were synthesized and characterized by spectroscopic means and elemental analysis.Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively.The ulcerogenicity was also determined for all the compounds.Some of the compounds showed moderate enhancement of the activity.Among the synthesized derivatives,compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.
文摘Tuberculosis（TB） is one of the most common and even fatal infectious diseases known to mankind.Millions of new cases are reported every year over the world,and one-third of the world＇s population is potentially infected with mycobacteria tuberculosis（MTB）.Research to develop novel anti-TB drugs led to the identification of several isatin-based antimycobacterial agents,among which a number of potential candidates displayed excellent antimycobacterial activity and were found to be free of cytotoxicity.This review outlines the advances in the application of isatin hybrids as antimycobacterial agents and the critical aspects of design and structure-activity relationship of these derivatives.
基金Supported by the National Key Project of Major Infectious Disease of China(No.2008ZX10003-006)the National S&T Major Special Project on Major New Drug Innovation, China(No.2009ZX09301-003)
文摘A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity, compared to the parent moxifloxacin, was designed, synthesized and characterized by 1H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. smegmatis CMCC 93202. Compounds 3a―3f, 5a, 5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis（MTB） H37Rv ATCC 27294 and MDR-MTB 09710. All the target com pounds[minimum inhibitory concentration（MIC）： 0.39―〉16 μg/mL] were far more active than rifampin（MIC： 2.0―〉256 μg/mL）, but less active than moxifloxacin（MIC： 0.1―1.0 μg/mL） against the three tested strains. The most active compounds 3a and 3c were found to be 2―64 fold more potent than isoniazid and rifampin against M. smegmatis CMCC 93202, 2 fold more potent than rifampin against MTB H37Rv ATCC 27294, and 16―〉64 fold more potent than ethambutol, isoniazid and rifampin against MDR-MTB 09710.
基金a grant from Shandong Provincial Education Department, No. J08LH54
文摘The present study observed the action of 1H-indole-2, 3-dione （isatin） on Bax protein expression in the substantia nigra of a Parkinson＇s disease animal model. Parkinson＇s disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine （MPTP） Bax protein expression was significantly reduced in isatin （100, 200 mg/kg）-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.
基金supported by the National Natural Science Foundation of China (Nos. 21172189, 21572196)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The functionalized spiro[indoline-3,40-pyrano[3,2-h]quinolines] were efficiently prepared in high yields from three-component reaction of 8-hydroxyquinoline, isatins and malononitrile or ethyl cyanoacetate in ethanol at room temperature for about 12 h in the presence of piperidine.
基金support from the National Natural Science Foundation of China(No.21772185)supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB20000000).
文摘An efficient asymmetric alkenylation between 3-vinylindoles and isatin derivatives was developed under catalysis of a chiral copper complex.A series of optically active 3-alkenyl-3-substituted oxindoles were obtained in excellent yields and stereoselectivities.The reaction mechanism was proposed and supported by DFT calculation.
