Isatin Groups Research Articles

Synthesis, Fluorescence, and Bioactivity of Novel Isatin Derivatives.

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

The effect and mechanism of novel methoxy curcumin analogs based on network pharmacology.

In this study, a series of novel compounds were synthesized by introducing the 3,4,5-trimethoxyphenyl and isatin groups into the monocarbonyl skeleton of curcumin. The possible biological activities and potential targets for these compounds were explored through network pharmacology. The results revealed that these compounds could significantly inhibit production of the inflammatory factors IL-6 and TNF-α, and suppress phosphorylation of the extracellular signal-regulated kinase (ERK) protein. Moreover, molecular docking experiments showed that the ERK protein was the potential target for these compounds. In summary, this study, through network pharmacology, presents a novel series of methoxy curcumin analogs as potent anti-inflammatory drugs.

Novel Mitochondrial and DNA Damaging Fluorescent Calix[4]arenes Bearing Isatin Groups as Aromatase Inhibitors: Design, Synthesis and Anticancer Activity

Breast cancer causes a high rate of mortality all over the world. Therefore, the present study focuses on the anticancer activity of new lower rim-functionalized calix[4]arenes integrated with isatin and the p-position of calixarenes with 1,4-dimethylpyridinium iodine against various human cancer cells such as MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the PNT1A healthy epithelial cell line. It was observed that compound 6c had the lowest values in MCF-7 (8.83 µM) and MDA-MB-231 (3.32 µM). Cell imaging and apoptotic activity studies were performed using confocal microscopy and flow cytometry, respectively. The confocal imaging studies with 6c showed that the compound easily entered the cell, and it was observed that 6c accumulated in the mitochondria.The Comet assay test was used to detect DNA damage of compounds in cells. It was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. In vitro human aromatase enzyme inhibition profiles showed that compound 6c had a remarkable inhibitory effect on aromatase. Compound 6c displayed a significant inhibition capacity on aromatase enzyme with the IC50 value of 0.104 ± 0.004 µM. Thus, not only the anticancer activity of the new fluorescent derivatives, which are the subject of this study, but the aromatase inhibitory profiles have also been proven.

1-Benzyl-3-[(4-meth-oxy-phen-yl)imino]-indolin-2-one.

The title compound, C22H18N2O2, is a Schiff base obtained by condensing p-arnisidine (4-meth-oxy-aniline) with N-benzyl-isatin (1-benzyl-1H-indole-2,3-dione), which crystallizes in the triclinic P space group. The benzyl and phenyl rings subtend dihedral angles of 76.08 (7) and 60.70 (6)°, respectively, with the isatin group. The imino C=N double bond exists in an E conformation.

Synthesis, Enzymatic Degradation, and Polymer-Miscibility Evaluation of Nonionic Antimicrobial Hyperbranched Polyesters with Indole or Isatin Functionalities

Most macromolecular antimicrobials are ionic and thus lack miscibility/compatibility with nonionic substrate materials. In this context, nonionic hyperbranched polyesters (HBPs) with indole or isatin functionality were rationally designed, synthesized, and characterized. Antimicrobial disk diffusion assay indicated that these HBPs showed significant antibacterial activity against 8 human pathogenic bacteria compared to small molecules with indole or isatin groups. According to DSC measurements, up to 20% indole-based HBP is miscible with biodegradable polyesters (polyhydroxybutyrate or polycaprolactone), which can be attributed to the favorable hydrogen bonding between the N–H moiety of indole and the C=O of polyesters. HBPs with isatin or methylindole were completely immiscible with the same matrices. None of the HBPs leaked out from plastic matrix after being immersed in water for 5 days. The incorporation of indole into HBPs as well as small molecules facilitated their enzymatic degradation with PETase from Ideonella sakaiensis, while isatin had a complex impact. Molecular docking simulations of monomeric molecules with PETase revealed different orientations of the molecules at the active site due to the presence of indole or isatin groups, which could be related to the observed different enzymatic degradation behavior. Finally, biocompatibility analysis with a mammalian cell line showed the negligible cytotoxic effect of the fabricated HBPs.

Preparation, characterization, antioxidant properties of novel Schiff bases including 5-chloroisatin-thiocarbohydrazone

Thanks to its pharmaceutical properties, the Schiff group of isatin has recently had a wide range of uses. In this study, seven new Schiff bases of isatin and its derivatives were prepared from thiocarbohydrazide, isatin and substituted aldehydes in the presence of ethanol under reflux. The chemical structures of the products were confirmed by 1H NMR, 13C NMR, IR and elemental analysis. The in vitro antioxidant features of all the compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl free radical scavenging method. The antioxidant effect was evaluated separately in two different stages: monosubstituted products synthesized with aldehyde groups and disubstituted products bound with isatin group. Accordingly, the compounds 3 and 4 showed the highest antioxidant activity and the isatin group suppressed the antioxidant effect of the disubstituted Schiff bases products.

Synthesis and application of a novel magnetic SBA-15 nanosorbent for heavy metal removal from aqueous solutions

In this work for the first time, magnetic nanoporous SBA-15 functionalized with isatin groups as a magnetic nanosorbent was applied for the simultaneous extraction of trace amounts of cadmium(II), nickel(II), lead(II), and zinc(II). The characterization of this nanosorbent was studied using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The effect of several factors such as pH, amount of sorbent, extraction time, type and volume of the eluent, sample volume, sorption capacity, and potentially interfering ions were investigated. In the selected conditions, it was observed that the limits of detection were 0.10 ng mL−1 for Cd(II), 0.25 ng mL−1 for Ni(II), 0.4 ng mL−1 for Pb(II), and 0.2 ng mL−1 for Zn(II), and the maximum sorption capacity of this suggested magnetic nanosorbent was 140, 122, 110, and 115 mg g−1 for Cd(II), Ni(II), Pb(II), and Zn(II), respectively. Finally, the suggested procedure was applied for determination of cadmium(II), nickel(II), lead(II), and zinc(II) at trace levels in different water and agricultural products with satisfactory results.

Synthesis and application of a novel magnetic nanosorbent for determination of trace Cd(II), Ni(II), Pb(II), and Zn(II) in environmental samples

In this work for the first time, Fe3O4@SiO2 core–shell nanoparticles functionalized with isatin groups as a magnetic nanosorbent was applied for the simultaneous extraction of trace amounts of cadmium(II), nickel(II), lead(II), and zinc(II). The characterization of this nanosorbent was studied using Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction, vibrating sample magnetometer and thermogravimetric analysis. The effect of several factors such as pH, amount of sorbent, extraction time, type and volume of the eluent, sample volume, sorption capacity, and potentially interfering ions was investigated. In the selected conditions, it was observed that the limits of detection were 0.11 ng mL−1 for Cd(II), 0.28 ng mL−1 for Ni(II), 0.47 ng mL−1 for Pb(II), and 0.21 ng mL−1 for Zn(II), and the maximum sorption capacity of this suggested magnetic nanosorbent was 120, 112, 100, and 100 mg g−1 for Cd(II), Ni(II), Pb(II), and Zn(II), respectively. Also, the precision of the method (RSD%) for ten replicate measurements was found 2.5, 2.5, 2.8, and 3.1%, for Cd(II), Ni(II), Pb(II), and Zn(II) ions, respectively. Finally, the suggested procedure was applied for determination of cadmium(II), nickel(II), lead(II), and zinc(II) at trace levels in different water and agricultural products with satisfactory results.

1-[(2E)-3-Phenylprop-2-en-1-yl]-1H-indole-2,3-dione

In the title compound, C17H13NO2, the indole ring is essentially planar (r.m.s. deviation = 0.027 Å) and is oriented at an angle of 69.33 (7)° with respect to the phenyl ring. In the crystal, C—H...O hydrogen bonds link the molecules, forming zigzag chains propagating along thea-axis direction. Within the chains there are π–π stacking interactions [centroid–centroid distances = 3.7163 (8) and 3.7162 (8) Å] involving isatin groups of neighbouring molecules.

Fully branched hyperbranched polymers with a focal point: analogous to dendrimers

A fully branched hyperbranched polymer with a focal point has been prepared by superelectrophilic polycondensation of AB2 monomers with a core with six functional arms (B6′) in a slow addition manner. To reduce the chance of the homopolymerization of the monomers, the acenaphthenequinone group with higher reactivity was chosen as B′ for the core and the isatin group with lower reactivity as B in the monomer. The obtained polymers were characterized by 1H NMR, 13C NMR, TGA and GPC. The thermo-decomposition temperature of the polymer could reach 400 °C. The NMR spectra indicated the 100% branching degree of the hyperbranched polymers and the successful introduction of the core. The proportions of the terminal/dendritic groups in the hyperbranched polymers with low monomer/core feeding ratio were evaluated through NMR and GPC data respectively. Through comparison and analysis it was revealed that most of the hyperbranched polymers possessed quasi-spherical structures. The molecular weights of the hyperbranched polymers increased almost linearly with the feeding ratio of the monomer to the core and the polydispersities of the polymers were greatly influenced by the monomer concentration. At the optimal monomer concentration, the main parts of the GPC curves were symmetric and narrow. Although there were traces of faint shoulder, the molecular weight distributions of the polymers were still acceptable. The branching degree of 100%, controllable molecular weights, narrow distribution, plus the quasi-spherical and hierarchical architectures of cores, dendritic and terminal units made the fully branched polymer with a focal point analogous to dendrimers in all respects, offering a highly efficient option to fabricate dendrimer substitutes.

1-Benzyl-3-[(4-methylphenyl)imino]indolin-2-one

In the title compound, C22H18N2O, the phenyl and tolyl rings make dihedral angles of 84.71 (7) and 65.11 (6)°, respectively, with the isatin group. The aromatic rings make a dihedral angle of 60.90 (8)°. The imino C=N double bond, exists in an E conformation. In the crystal, mol­ecules are linked by weak π–π stacking inter­actions [centroid–centroid distance = 3.6598 (13) Å].

Tunability of anion binding strength based on acyl-thiourea receptors containing isatin group

Some acyl-thiourea derivatives containing isatin group were synthesized and their interactions with anions were investigated using UV–vis spectroscopy and 1H NMR titrations in DMSO and DMSO- d 6, respectively. These compounds have a same molecular framework, functionalising with different groups lead to different anion binding strength of these receptors. Receptor 1 showed a higher binding affinity for AcO − than for F −, due to the cooperative multiple hydrogen bond interactions of AcO − with the acyl-thiourea group and N–H group in the indole unit of receptor 1. Displacing the N–H proton in the indole unit with –CH 3 group, receptor 2 showed no obviously discriminative responses for F −, AcO − and H 2PO 4 − due to lack of such additional binding. In the case of receptor 3, which was functionalised with strong electron-withdrawing group, it showed selectively chromogenic response for F − based on double deprotonation of the receptor in DMSO, whereas AcO − and H 2PO 4 − induced single deprotonation only.

N-Benzylindole-2,3-dione (N-benzylisatin)

The title molecule, C15H11NO2, is non-planar, the dihedral angle between the isatin group and the phenyl ring being 87.08 (5)°. The crystal structure is stabilized by C–H...O hydrogen bonding interactions.

Inhibition of granulocyte-macrophage colony formation in vitro by substituted isatin thiosemicarbazones.

The 1-methylisatin derivative of isatin thiosemicarbazone was previously shown to inhibit granulocyte-macrophage colony growth in vitro by an action at the early stages of colony development. The parent compound isatin thiosemicarbazone and 25 other derivatives were tested, and a wide range of activity was found (50% colony inhibition from 0.07 to > 100 mug per ml of culture). High activity was not associated with any specific substituent although 1-methyl or 1-ethyl isatin groups in association with 4'4' morpholino or 4'4' tetramethylene thiosemicarbazone substitutions were within the most active group. No correlation between the antimarrow and known antiviral activities of these compounds was apparent. Two of the more active compounds were compared with methisazone and were shown to have the same property of selective action on the early stages of granulocyte-macrophage differentiation in culture. It is suggested that this group of compounds might possibly provide some useful antileukemia agents.

Effect of Heterocyclic and Other Thiosemicarbazones on Vaccinia Infection in the Mouse

Summary Thiosemicarbazones containing benzene, thiophene, pyridine, quinoline or isatin groups have been demonstrated to protect mice against vaccinia virus. Protection is obtained when the virus is given by the cerebral route and compounds fed in the diet. The =N-NH-CS-NH2 group, as such, appears to be essential for antivaccinal activity. Semicarbazones of benzaldehyde, 2-thenaldehyde, cinchoninaldehyde and isatin were devoid of protective capacity. The presence of an aldehyde structure with attachment of the thiosemicarbazone moiety to the aldehyde carbon atom contributes to antiviral capacity but is not essential for this property. Substitutions on the aldehyde carbon atom reduced or abolished protective action of compounds. Substitution in the ring protion of the molecule produced the same result except in p-nitro and o-methoxy benzaldehyde and 5-chloro, 5-bromo and 3-methyl-2-thenaldehyde derivatives. Thiosemicarbazones with high antivaccinal activity in mouse embryonic tissues may fail to protect mice against the virus.