- Molecular modeling and in vitro studies of a neutral oxime as a potential reactivator for acetylcholinesterase inhibited by paraoxon
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The present work aimed to compare the small, neutral and monoaromatic oxime, isatin-3-oxime (isatin-O), to the commercial ones, pralidoxime (2-PAM) and obidoxime, in a search for a new potential reactivator for acetylcholinesterase (AChE) inhibited by the pesticide paraoxon (AChE/POX) as well as a novel potential scaffold for further synthetic modifications. The multicriteria decision methods (MCDM) allowed the identification of the best docking poses of those molecules inside AChE/POX for further molecular dynamic (MD) studies, while Ellman’s modified method enabled in vitro inhibition and reactivation assays. In corroboration with the theoretical studies, our experimental results showed that isatin-O have a reactivation potential capable of overcoming 2-PAM at the initial moments of the assay. Despite not achieving better results than obidoxime, this molecule is promising for being an active neutral oxime with capacity of crossing the blood–brain barrier (BBB), to reactivate AChE/POX inside the central and peripheral nervous systems. Moreover, the fact that isatin-O can also act as anticonvulsant makes this molecule a possible multipotent reactivator. Besides, the MCDM method showed to be an accurate method for the selection of the best docking poses generated in the docking studies.
- de Paula, Reuel L.,de Almeida, Joyce S.F.D.,Cavalcante, Samir F.A.,Gon?alves, Arlan S.,Simas, Alessandro B.C.,Franca, Tanos C.C.,Valis, Martin,Kuca, Kamil,Nepovimova, Eugenie,Granjeiro, José M.
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- Pronounced ionic liquid effect in the synthesis of biologically active isatin-3-oxime derivatives under acid catalysis
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An efficient method was developed for the preparation of isatin-3-oxime derivatives with Bronsted and/or Lewis acids in imidazolium-based ionic liquids. Isatin-3-oxime bearing the electron donating methoxy group was equally obtained in good yields. The pr
- Pinto, Angelo C.,Lapis, Alexandre A. Moreira,da Silva, Barbara Vasconcellos,Bastos, Renato S.,Dupont, Ja?rton,Neto, Brenno A.D.
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Read Online
- The benzonitrile derivative
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[A] suppressing the generation of impurities caused by side reactions and reaction, and benzonitrile derivative can be obtained in high purity of the benzonitrile derivative method. The compound represented by general formula [a] I, III and IV compound represented by general formula compound represented by a general formula selected from the group consisting of tertiary amines in the presence of at least 1 species is reacted, the benzonitrile derivative represented by general formula II comprises obtaining the benzonitrile derivative. In the general formula I, R1 - R4 Each independently, a hydrogen atom, an alkyl group of carbon number 1 - 5 represent the like, in the general formula II, R21 - R24 Each independently, a hydrogen atom, an alkyl group of carbon number 1 - 5 represent the like, in the general formula III, R31 - R33 Is, each independently represents an alkyl group or a phenyl group, having the general formula IV in, R41 - R44 Is, each independently represents an alkyl group. The details of the code as described herein. [Drawing] no
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Paragraph 0048-0049
(2021/10/08)
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- Synthesis and evaluation of isatin derivatives as antifungal agents
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Various types of isatin derivatives were synthesized by reacting isatin with different reagents viz substituted acetophenones, sodium nitrate, hydroxylamine hydrochloride and hydrazine hydrate. Characterization of the synthesized compounds was done by using various spectral techniques such as IR,1HNMR,13CNMR, elemental analysis and mass spectrometry. Synthesized compounds were further evaluated for their antifungal activity against Helminthosporium oryzae, Rhizoctonia solani and Fusarium moniliforme using poison food technique. 3-(2-Oxo-2-phenylethylidene) indolin-2-one showed significant mycelium inhibition against all tested rice fungi.
- Dawar, Monika,Kaur, Komalpreet,Rani, Ritu,Utreja, Divya
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p. 199 - 205
(2020/02/29)
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- 1,3-Dipolar Cycloaddition of 3-Amino Oxindole-Based Azomethine Ylides and O-Vinylphosphonylated Salicylaldehydes for Diastereoselective Synthesis of Oxindole Spiro-P, N-polycyclic Heterocycles
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An efficient stereoselective assembly strategy for the construction of pyrrolidin-2,3′-oxindole cis-fused phosphadihydrocoumarins was established. The process involves the condensation of O-vinylphosphonylated salicylaldehydes and 3-amino oxindoles followed by intermolecular cycloaddition with high diastereoselectivity and atom economy.
- Huang, Tiao,Kong, Dulin,Liu, Li,Wang, Qinghe,Wu, Mingshu
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supporting information
p. 1387 - 1397
(2020/04/27)
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- Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate
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Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
- Cavalcante, Samir F. de A.,Kitagawa, Daniel A.S.,Rodrigues, Rafael B.,Bernardo, Leandro B.,da Silva, Thiago N.,dos Santos, Wellington V.,Correa, Ana Beatriz de A.,de Almeida, Joyce S.F.D.,Fran?a, Tanos C.C.,Ku?a, Kamil,Simas, Alessandro B.C.
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- Copper-Catalyzed Carbonyl Group Controlled Coupling of Isatin Oximes with Arylboronic Acids To Prepare N-Aryloxindole Nitrones
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A variety of (E)-N-aryloxindole nitrones were prepared in good to excellent yields by using a copper-catalyzed coupling reaction of isatin oximes and arylboronic acids under mild conditions. Various arylboronic acids that contain sensitive functional groups were tolerated in the transformation, and detailed studies show that the carbonyl group of the isatin oximes serves as a ligand to control the formation of the (E)-oxindole nitrones. This method to prepare (E)-N-aryloxindole nitrones was easily performed on a gram scale and efficiently used to synthesize estrone-derived oxindole nitrone in high yield.
- Mo, Xue-Ling,Chen, Chun-Hua,Liang, Cui,Mo, Dong-Liang
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p. 150 - 159
(2017/11/28)
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- Synthesis of N-Aryl Oxindole Nitrones through a Metal-Free Selective N-Arylation Process
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An efficient selective N-arylation of 3-(hydroxyimino)indolin-2-ones with diaryliodonium salts to prepare (Z)-N-aryl oxindole nitrones has been achieved under simple base-mediated conditions. The reaction tolerated a variety of diaryliodonium salts with diverse and sensitive functional groups. Studies on the oxime structures revealed that the pyrroline ring and carbonyl group in 3-(hydroxyimino)indolin-2-ones played important roles in the selective N-arylation process. The N-aryl oxindole nitrones could be prepared rapidly and easily at the gram scale.
- Wu, Si-Yi,Ma, Xiao-Pan,Liang, Cui,Mo, Dong-Liang
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p. 3232 - 3238
(2017/03/23)
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- Metal-free synthesis of isatin oximes: Via radical coupling reactions of oxindoles with t -BuONO in water
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A metal-free method for the synthesis of isatin oximes was developed through the radical coupling reactions of oxindoles with t-BuONO. This protocol provides a practical and environmentally benign method for the construction of C-N bonds in water at room temperature without using any other reagents. The advantages of this strategy are its mild reaction conditions and clean procedure.
- Wei, Wen-Ting,Zhu, Wen-Ming,Ying, Wei-Wei,Wu, Yi,Huang, Yi-Ling,Liang, Hongze
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supporting information
p. 5254 - 5257
(2017/07/10)
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- A isatin - 3 - oxime derivatives of the preparation method (by machine translation)
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The invention discloses a isatin - 3 - oxime derivatives of the preparation process, the method to 2 - indolone derivatives as raw materials, the water as a solvent, and nitrous acid tert-butyl at room temperature and under the condition of air reaction to obtain high yield and purity of the isatin - 3 - oxime derivatives. The method of the invention does not use the metal reagent, with synthetic and post treatment process is simple, low cost, environment-friendly advantages. (by machine translation)
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Paragraph 0023-0029
(2017/10/07)
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- Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as multi-targeted compounds against Alzheimer's disease
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A series of benzoates (or phenylacetates or cinnamates) - tacrine hybrids (7a-o) were designed, synthesized and evaluated as multi-potent anti-Alzheimer drug candidates. The screening results showed that most of them exhibited a significant ability to inhibit ChEs, certain selectivity for AChE over BuChE and strong potency inhibitory of self-induced β-amyloid (Aβ) aggregation. All IC50 values of biological activity were at the nanomolar range. Especially, compound 7c displayed the greatest ability to inhibit AChE with an IC50 value of 5.63 nM and the highest selectivity with ratio of BuChE/AChE value of 64.6. Moreover, it also exhibited a potent inhibitory of Aβ aggregation with an IC50 value of 51.81 nM. A Lineweaver-Burk plot and molecular modeling study showed that compound 7c targeted both the CAS and PAS of ChEs. A structure-activity relationship analysis suggested that the electron density of aromatic ring which was linked with tacrine through acetyl group played a significant role in determining the inhibitory activity.
- Zhang, Chao,Du, Qiao-Yi,Chen, Lang-Di,Wu, Wen-Hao,Liao, Si-Yan,Yu, Li-Hong,Liang, Xin-Tong
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supporting information
p. 200 - 209
(2016/04/19)
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- Synthesis, cytoprotective and anti-Tumor activities of Isatin Schiff bases
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A series of simple isatin Schiff bases were synthesized through the condensation reaction. These isatin Schiff bases were characterized by NMR and MS, and the structure was discussed. Then, the cytoprotective and anti-Tumor activities of these compounds were evaluated. The results show that several compounds show protection activity on the apoptosis of PC12 cells induced by H2O2, which are more effective than that of (±) α-Tocophreol (VE) and isatin. Besides, some compounds also show more potent anti-Tumor activity against A549 and P388 cell lines than that of isatin.
- Chen, Gang,Meng, Mei,Zhang, Yu,Hao, Xiaojiang,Wang, Ye,Mu, Shuzhen
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p. 802 - 805
(2015/11/18)
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- Action of Hydrazines on 2-(2-Oxindolin-3-ylidene)malononitrile, (E,Z)-Ethyl 2-cyano-2-(2-oxindolin-3-ylidene)acetate and Isatin-β-thiosemicarbazone as a Source of Spiro Indoline-pyrazole Systems
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2-(2-Oxindolin-3-ylidene)malononitrile (1a) or (E,Z)-ethyl 2-cyano-2-(2-oxindolin-3-ylidene)acetate (1b) or isatin-β-thiosemicarbazone (1c) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline-2-one moiety (2). The hydrazone derivatives (2) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives (3a, 3b). Also, cinnoline derivative (9) is obtained by action of hydrazine hydrate on the N-acetyl derivative of (6a). The structures of the newly synthesized compounds were evaluated by IR, 1H-NMR spectroscopy, mass spectra and elemental analyses.
- Youssef, Ahmed S. A.,Hemdan, Magdy M.,Emara, Samir A.,Kamel, Rabaa M.
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p. 1331 - 1336
(2015/10/06)
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- A novel strategy to the synthesis of 4-anilinoquinazoline derivatives
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A novel approach to prepare 4-anilinoquinazoline derivatives based on the transformation of indoline-2,3-dione to formamidine was developed. The processes with this approach are simple, efficient, and environmentally friendly. The efficiency of this approach was evaluated by synthesizing 17 4-anilinoquinazolines and comparing the obtained yields with those achievable through conventional synthetic methods. It was the first time that compounds 8d, 8e, 8h, and 13b-f were synthesized. The characteristics of the IR and the UV spectra of these compounds and the effects of their substituents on the spectra were observed.
- Wang, Zheng,Wang, Cuiling,Sun, Yanni,Zhang, Ning,Liu, Zhulan,Liu, Jianli
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p. 906 - 913
(2014/01/23)
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- Discovery and structure optimization of a series of isatin derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors
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In this study, the crystal structure of the Mycobacterium tuberculosis (MTB) enzyme chorismate mutase (CM) bound to transition state analogue (PDB: 2FP2) was used as a framework for virtual screening of the BITS-Pilani in-house database (2500 compounds) to identify new scaffold. We identified isatin as novel small molecule MTB CM inhibitors; further twenty-four isatin derivatives were synthesized and evaluated in vitro for their ability to inhibit MTB CM, and activity against M. tuberculosis as steps towards the derivation of structure-activity relationships (SAR) and lead optimization. Compound 3-(4-nitrobenzylidene)indolin-2-one, 24 emerged as the most promising lead with an IC50 of 1.01 ± 0.22 μm for purified CM and MIC of 23.5 μm for M. tuberculosis, with little or no cytotoxicity. 2D interaction profile of compounds 1, 7 and 25 with the active site residues.
- Jeankumar, Variam U.,Alokam, Reshma,Sridevi, Jonnalagadda P.,Suryadevara, Priyanka,Matikonda, Siddharth S.,Peddi, Santosh,Sahithi, Seedarala,Alvala, Mallika,Yogeeswari, Perumal,Sriram, Dharmarajan
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p. 498 - 506
(2014/05/06)
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- Synthesis and evaluation of isatin derivatives as corrosion inhibitors for Q235A steel in highly concentrated HCl
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A series of inhibitors - isatin derivatives aimed at anticorrosion of Q235A steel - was synthesized. The molecule structures were analyzed by NMR and MS. The inhibition on the corrosion in a concentrated HCl solution as high as 3 M was studied by weight loss, molecular simulation, and potentiodynamic polarization. The results indicate that isatin derivatives act as mixed type (cathodic/anodic) inhibitors. Several compounds were investigated in the formulations, during which compound 6 shows 95.5 % inhibition efficiency under the concentration of 100 mg/L accompanied by urotropine and 1,4-dihydroxy-2- butyne.
- Chen, Gang,Su, Hui-Jun,Song, Ying-Pan,Gao, Yu,Zhang, Jie,Hao, Xiao-Jiang,Zhao, Jing-Rui
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p. 3669 - 3678
(2013/10/22)
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- Novel isatinoxime molybdenum and chromium complexes: Synthesis, spectroscopic, and thermal characterization
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Reactions of molybdenum and chromium hexacarbonyls with isatin-3-oxime (H2L) in THF were carried out under sun light or according to the traditional thermal reflux synthetic routes. Di-μ-oxo bimolybdenum complex, [Mo(H2L)(THF)(O)sub
- Nassar, Mostafa Y.,Attia, Attia S.,Adawy, Shaymaa,El-Shahat, M. F.
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p. 88 - 92,5
(2012/12/11)
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- Efficient microwave-assisted synthesis of oximes from acetohydroxamic acid and carbonyl compounds using BF3·OEt2 as the catalyst
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An efficient synthesis of oximes by reaction of carbonyls with acetohydroxamic acid using BF3·OEt2 as a catalyst is described.
- Sridhar, Madabhushi,Narsaiah, Chinthala,Raveendra, Jillella,Kondal Reddy, Godala,Kishore Kumar Reddy, Mallu,China Ramanaiah, Beeram
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experimental part
p. 4701 - 4704
(2011/09/20)
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- Synthesis and in vitro antimycobacterial activity of 8-OCH3 ciprofloxacin methylene and ethylene isatin derivatives
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A series of novel 8-OCH3 ciprofloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity were synthesized in this study. These derivatives were evaluated for their in vitro activity against some mycobacteria. All of the synthesized compounds were less active than the parent 8-OCH3 ciprofloxacin against Mycobacteriumsmegmatis CMCC 93202, but most of the methylene isatin derivatives were more active than 8-OCH3 ciprofloxacin, ciprofloxacin, isoniazid and rifampin against MTB H37Rv ATCC 27294. It was noted that compound 3b (MIC: 0.074 μM) was 2-13 fold more potent than the reference compounds against MTB H37Rv ATCC 27294, and compounds 3f and 3i-k (MIC: 6.72-7.05 μM) were around 1.6 fold more potent than the parent 8-OCH3 ciprofloxacin, 3.5 fold more potent than ciprofloxacin against MDR-MTB 09710.
- Feng, Lian-Shun,Liu, Ming-Liang,Zhang, Shu,Chai, Yun,Wang, Bo,Zhang, Yi-Bin,Lv, Kai,Guan, Yan,Guo, Hui-Yuan,Xiao, Chun-Ling
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experimental part
p. 341 - 348
(2011/02/25)
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- Acylating and arylsulfonylating ability of O-derivatives of isatin 3-oximes
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O-Acyl and O-arylsulfonyl derivatives of isatin 3-oximes have been synthesized and their interaction with alcohols and amines has been investigated. It was established that none of the esters of 1-substituted isatin 3-oximes reacted with the indicated nucleophiles. 1-Unsubstituted O-aryl and O-arylsulfonyl derivatives react with amines as acylating agents even at room temperature, but O-acetyl derivatives only on heating. Acylamides or arylsulfamides respectively are formed in this way. O-Acyl derivatives do not react with alcohols at room temperature. Only O-benzoyl derivatives form ethyl benzoate on heating in ethanol. A comparative analysis of mass spectrometric data on the processes of acylation and arylsulfonylation is given.
- Stankevicius,Terentiev,Janushene,Savickas
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- Synthesis and pharmacological studies of 1-p-nitrobenzoyl-3-(3-substituted-2-hydroxypropyloximino) indole-2,3-diones
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Sodium salt of 3-oximino indole-2,3-dione on reaction with epichlorohydrin in N,N′-dimethylformamide gives 3-(2,3-epoxypropyloximino) indole-2,3-dione 2. Compound 2 on reaction with diverse secondary amines yields corresponding Mannich bases 3a-e, which on benzoylation furnish 4a-e. The synthetic benzoyl derivatives of 4a-e have been screened for their pharmacological activities.
- Padhy,Panda,Sahu,Misro
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p. 258 - 261
(2007/10/03)
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- Synthesis of isatin 3-oximes from 2-nitroacetanilides
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2-Nitroacetanilides, prepared by alkaline hydrolysis of 1-arylamino-1-methylthio-2-nitroethenes, are converted into isatin (1H-indole-2,3-dione) 3-oximes by treatment with concentrated sulfuric acid or trifluoromethanesulfonic acid at room temperature.
- Kearney,Harris,Jackson,Joule
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p. 769 - 772
(2007/10/02)
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- SEMICARBAZONES AND THIOSEMICARBAZONES OF THE HETEROCYCLIC SERIES. XLVII. ACYLATION OF ISATIN
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Contrary to previous data, the acylation of isatin by carboxylic acid anhydrides in the presence of perchloric acid leads to the formation not of the O-acyl derivatives but of the N-acyl derivatives, which have a noncoplanar structure.Their transformation into isatin hydrazone and oxime is due to hydrolysis of the N-acyl group.In alcohol solutions the N-acylisatins rapidly open the five-membered ring with the addition of an alcohol molecule.
- Tomchin, A. B.,Fradkina, S. P.,Krylova, I. M.,Khromenkova, Z. A.
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p. 2163 - 2172
(2007/10/02)
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- A STUDY OF THE PREPARATION AND REACTIONS OF THE UNUSALLY LABILE 5-METHYLOXADIAZOLOQUINAZOLIN-2-ONE
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A ?2s + ?2s + ω2s cycloaddition of 4-isocyanato-2-methyl quinazoline 3-oxide leads to the title compound, 5-methyloxadiazoloquinazolin-2-one (1).Surprisingly, the weakest bond in 1 is 4-5.Rupture of this bond takes place thermally as well as with P(OR)3 leading to the isomeric, 5-methyloxadiazoloquinazolin-3-one (11).A detailed thermolytic study of 1 has given products arising from scission of the bonds 2-3, 3-4- and 4-5.The 3-4 bond is preferentially broken on photolysis of 1 in MeOH.
- Ranganathan, Darshan,Bamezai, Shakti,Ramachandran, Veeraraghavan
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p. 623 - 632
(2007/10/02)
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