N-substituted Isatin Research Articles

Synthesis and crystal structure of new monometallic and bimetallic copper(II) complexes with N-substituted isatin thiosemicarbazone ligands: Effects of the complexes on DNA/protein-binding property, DNA cleavage study and in vitro anticancer activity

A novel series of N-substituted isatin thiosemicarbazone ligands (L1–L3) and their copper(II) complexes [Cu(II)(ITSC)] were synthesized and characterized by elemental analyses and UV–Vis, FT-IR, 1H &13C NMR/EPR and mass spectroscopic techniques. The molecular structures of L1, L2, L3, 2 and 3 were confirmed by single crystal X-ray crystallography. The X-ray diffraction studies of the complexes 2 and 3 reveal the square planar and square pyramidal geometry. The binding affinity and binding mode of the monometallic and bimetallic complex toward calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were determined by UV–Vis and fluorescence spectrophotometric methods. Spectral evidences show intercalative mode of DNA binding with the copper(II) complexes. Complexes (1, 2 and 3) cleaved the pUC19 plasmid DNA in the absence of an external agent. An in vitro cytotoxicity study of the complex 3 found good activity against human breast (MCF7) and lung (A549) cancer cell lines.

Synthesis of substituted pyrazolo[3,4-d]pyrimidines by reactions of 5-amino-1-phenyl-1H-pyrazole derivatives with N-substituted isatins

The reaction of N-substituted isatins with 5-amino-1-phenyl-1H-pyrazole-4-carboxamide in refluxing methanol in the presence of excess sodium methoxide led to cyclocondensation with the formation of 1-R-1'-phenyl-1',7'-dihydrospiro[indole-3,6'-pyrazolo[3,4-d]pyrimidine]-2,4'(1H,5'H)-diones. Analogous reaction with 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile was a cascade process that involved the formation of 1-R-4'-(methoxy)-1'-phenyl-1',7'-dihydrospiro[indole-3,6'-pyrazolo[3,4-d]pyrimidine]-2(1H)-ones as intermediates and led to N-R-2-[4-(methoxy)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]anilines.

Synthesis and bio-evaluation of quaternary centered 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives for anticancer and antimicrobial activities

A series of C(3)-trifluoromethylated compounds derived from N-substituted isatins were synthesized. The biological activity of all 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives have been evaluated for in vitro cytotoxic activity and antibacterial activity. The active compounds were screened against nuclear xenobiotic receptor CAR (PDB ID: 1XLS), PIM1 kinase (PDB ID: 2O65), and CDK2 kinase (PDB ID: 3QHR) by using in silico molecular docking studies to obtain lead molecules. In addition to its potential anticancer activity, 5-bromo-3-ethynyl-3-hydroxy-1-(prop-2-yn-1-yl)indolin-2-one also showed specific antibacterial activity against S. aureus.

Organocatalytic Asymmetric Biginelli-like Reaction Involving Isatin.

The first asymmetric, Brønsted acid catalyzed Biginelli-like reaction of a ketone has been developed, employing N-substituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. BINOL-derived phosphoric acid catalysts have been used to achieve the synthesis of a small library of chiral, enantioenriched spiro(indoline-pyrimidine)-diones derivatives. The absolute configuration of the new spiro stereocenter was assessed on diastereoisomeric derivatives through computer-assisted NMR spectroscopy. X-ray diffractometry allowed the disclosure of the overall molecular conformation in the solid state and the characterization of the crystal packing of a Br-substituted Biginelli-like derivative, while computational studies on the reaction transition state allowed us to rationalize the stereochemical outcome.

Synthesis, X-ray crystal structure, DNA/protein binding and DNA cleavage studies of novel copper(ii) complexes of N-substituted isatin thiosemicarbazone ligands

Copper(ii) complexes containing isatin thiosemicarbozone ligands have been synthesized and evaluated for its biological applications like DNA/protein binding and DNA cleavage studies.

Imidazolidinone based chiral auxiliary mediated acetate aldol reactions of isatin derivatives and stereoselective synthesis of 3-substituted-3-hydroxy-2-oxindoles

Acetate aldol reactions of (S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one chiral auxiliary have been optimized with high yields and diastereoselectivity on various N-substituted isatins. The standardized reaction condition was employed for the stereoselective synthesis of furoindolines, and the pyrroloindole based natural products flustraminol B and N-benzyl alline.

Synthesis, Anti-tumor Activity and Odd–even Effect of Simple Isatin Derivatives

In this work, a series of N-substituted isatin derivatives was synthesized by different reactions. The synthesized isatin derivatives were characterized by NMR, MS and elemental analysis. Then the anti-tumor activities of these compounds were evaluated through the cytotoxicity against A549 and P388 cell line test. The results show that several compounds show much higher anti-tumor activity than that of isatin, and there is an even-odd effect in the structure activity relationship.

A cascade synthetic route to new bioactive spiroindolinepyrido[1,2-a]indolediones from indirubin

The allylation of indirubin produced the expected indolic N′-allylindirubin and N,N′-diallylindirubin derivatives in moderate yields, together with the corresponding N-substituted isatin products. At higher temperatures, the base-initiated reaction with allylic halides yielded spiroindolinepyrido[1,2-a]indolediones in a one-pot cascade reaction sequence with yields of up to 70%. These readily accessed, new spiro compounds represent the first reported examples of indirubin participating in cascade reactions. Preliminary in vitro biological testing of some of the products indicated promising activity against some cancer cell lines and against Plasmodium falciparum for two spiro derivatives. Computational methods were used to gain a greater understanding of the UV/Vis spectroscopic data for the N′-substituted and N,N′-disubstituted indirubin derivatives.

Synthesis of 3,3-dichloro-2-oxindoles from isatin-3-p-tosylhydrazones and (dichloroiodo)benzene

A series of aryl- and N-substituted isatin derivatives were converted to the corresponding isatin-3-p-tosylhydrazones, and these were subjected to a Lewis base-catalyzed chlorination reaction that employs the hypervalent chlorinating agent PhICl2. The discovery of p-tosylhydrazones as chlorination precursors has expanded the functional group tolerance of the chlorination reaction to now include carbamates, acetamides, and sulfonates. Additionally, this allowed us to circumvent the use of the diazo group in our chlorination reaction, and offers a new avenue for exploring our two-step deoxygenative dihalogenation reaction. We also disclose the use of PhICl2 for the oxidative chlorination of sulfinates to the corresponding sulfonyl chlorides.

FeCl3-Catalyzed Combinatorial Synthesis of Functionalized Spiro[Indolo-3,10'-indeno [1,2-b]quinolin]-trione Derivatives.

An efficient, inexpensive, environmentally friendly and high yield one-pot route to new spiro[indolo-3,10'-indeno [1,2-b]quinolin]-trione derivatives has been developed, involving three-component reaction of enaminones, N-substituted isatins and Indane-1,3-dione catalyzed by FeCl3. The approach to this spiro-heterocycle is noteworthy because it results in the formation of three new σ (two C-C and one C-N) bonds in a single operation, leading to the construction of novel spiro skeleton. This method works on a large scale in excellent yields.

Asymmetric Organocatalytic Aza-Michael Reactions of Isatin Derivatives

Isatin was activated by derivatization to a Schiff base with aniline and used as an aza-Michael donor in organocatalytic asymmetric reactions with symmetric and nonsymmetric unsaturated 1,4-diketones. After hydrolysis (in situ), the N-substituted isatins were obtained in high yields (up to >95%) with high enantioselectivity (up to 95%).

Synthesis, DNA/protein binding, molecular docking, DNA cleavage and in vitro anticancer activity of nickel(ii) bis(thiosemicarbazone) complexes

Cytotoxic nickel(ii) complexes with an N-substituted isatin thiosemicarbazone were synthesized and their interaction with CT DNA and BSA protein was investigated, which was supported by molecular docking studies.

2,1-Benzothiazine 2,2-Dioxides. 8*. Synthesis and Structure of 2'-Amino-2-Oxo-1,2-Dihydro-6'H-Spiro-[Indole-3,4'-Pyrano[3,2-c][2,1]Benzothiazine]-3'-Carbonitrile 5',5'-Dioxides

2,2-Dioxides of 1-R-1H-2,1-benzothiazin-4(3H)-ones easily undergo a three-component condensation with N-substituted isatins and malononitrile in the presence of triethylamine giving 6'-R-1-R1-2'-amino-2-oxo-1,2-dihydro-6'H-spiro[indole-3,4'-pyrano[3,2-c][2,1]benzothiazine]-3'-carbonitrile 5',5'-dioxides in good yields. The reaction with 1-unsubstituted 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide follows an analogous route, but the products are triethylammonium salts of the corresponding spiro compounds.

Palladium-Catalyzed Interceptive Decarboxylative Addition of Allyl Car­bonates with Carbonyl Group

The first palladium-catalyzed interceptive decarboxylative 1,4-addition of allyl carbonates with squarates is reported. Interestingly, the C-3 carbonyl group of N-substituted isatins undergoes smooth decarboxylative 1,2-addition with allyl carbonates. This transformation offers a straightforward method for the synthesis of spiro-oxepane-fused 2-oxindole.

Employing Arynes in Transition-Metal-Free, N-Heterocycle- Initiated Multicomponent Reactions

Transition-metal-free multicomponent reactions involving arynes, N-heterocycles, and various carbonyl compounds have been reported. With (iso)quinoline as the nucleophile and carbonyl compounds, such as aldehydes, ketones, and N-substituted isatins as electrophiles, the reaction afforded oxazino (iso)quinoline derivatives and the reaction proceeded via 1,4-dipolar intermediates. Interestingly, when the nucleophilic trigger used is pyridine, the reaction furnished indolin-2-one derivatives, and it is probable that the reaction proceeds via a pyridylidene intermediate.

An easy and efficient protocol for the condensation reaction of isatin and N-substituted isatins with 1,2-diaminobenzene using low cost reusable clay catalyst

Abstract A green procedure was developed for the condensation of isatin and N-substituted isatins with 1,2-diaminobenzene by using reusable bentonite clay in EtOH/H2O solvent system, under microwave irradiation. This eco-friendly synthesis is characterized by high yields and short reaction times. The catalyst is easily recycled.

Copper-catalyzed tandem oxidative cyclization of arylacetamides: efficient access to N-functionalized isatins

An efficient copper-catalyzed synthesis of N-substituted isatins has been developed in good yields from easily accessible arylacetamides. A wide range of electronically and structurally varied nitrogen fragments could be assembled through this tandem C–O/C–N bond-forming process by tuning the reaction conditions.

Synthesis and cytotoxic activity of some 2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)acetamide derivatives

Isatin, 1H-indoline-2,3-dione, an endogenous compound, is also a synthetically versatile molecule that possesses a diversity of biological activities including anticonvulsant, antibacterial, antifungal, antiviral, anticancer, and cytotoxic properties. Based on the promising cytotoxic activity studies on N-substituted isatin derivatives, a series of 18 derivatives of 2-(2,3-dioxo-2,3-dihydro- 1H-indol-1-yl)-N-phenylacetamide were designed, synthesized, and characterized according to their analytical and spectral data. All of the compounds were evaluated for their cytotoxic activity against MCF7, A549, HeLa, and HEK293 cell lines by real time cell analyzer. Etoposide was used as a standard compound. Briefly, ortho substitutions gave better results compared to meta and para substitutions on the N-phenyl ring and compounds bearing ortho substitutions were more effective on MCF7 cell lines than A549 and HeLa cell lines. 2-(2,3-Dioxo-2,3-dihydro-1H-indol-1-yl)-N- (2-isopropylphenyl)acetamide was the most active compound against all the tested cell lines.

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

A mild and practical synthesis of spirooxindole [1,3]oxazino derivatives from N-substituted isatins and 1,3-dicarbonyl compounds with pyridine derivatives is reported. The reactions provided good to excellent yields. Further exploration of the molecular diversity of these compounds is demonstrated through Diels–Alder reactions.

Synthesis and in vitro antibacterial activity of schiff bases of N-substituted isatins as effective scaffolds

Novel Schiff bases of N-substituted isatin, 1–13, were synthesized starting from isatin and N-(4-amino-2-methylphenyl)-4-chlorophthalimide and their structures were confirmed by spectral and elemental analyses. All new compounds were tested for their in vitro antibacterial activity against a range of Gram +ve bacterial strains, like Bacillus subtilis (NCIM-2156), Staphylococcus aureus (NCIM-2079) and Staphylococcus epidermis (NCIM-2493) and Gram −ve bacterial strains, like Pseudomonas aeruginosa (NCIM-2036),Escherichia coli (NCIM-2065) and Proteus vulgaris (NCIM-2027) following broth dilution method as recommended by the National Committee for clinical laboratory standards using ciprofloxacin as reference. Determination of minimum inhibitory concentration (MIC) and zone of inhibition showed that the molecules were more active against Gram −ve bacteria than Gram +ve bacteria. The compounds showed promising antibacterial properties with MIC ranging between 10 and 30 μg/mL.