Synthesis of novel spirooxindole-pyrrolidines and evaluation of their cytotoxic activity

Tumskiy, Roman S.; Burygin, Gennady L.; Anis’kov, A. A.; Klochkova, Iraida Nikolaevna

doi:10.1016/j.pharep.2018.12.004

Cited by 17 publications

(8 citation statements)

References 12 publications

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“…Nitrogen‐containing heterocyclic compounds are widely present in drugs and biologically active compounds, thus incorporation of multiple structural units of this type into a candidate drug molecule can improve biological activity and pharmacological properties. [ 1 ] In particular, the spirooxindole motif is often found in medicinally relevant compounds that exhibit important biological activity such as cytotoxic, [ 2 ] anticancer, [ 3 ] antitumor, [ 4 ] antidiabetic, [ 5 ] and anti‐amyloidogenic [ 6 ] activities. Dihydropyridines are well‐known effective calcium channel blocker drugs for the treatment of hypertension and cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Nickel supported on magnetic biochar as a highly efficient and recyclable heterogeneous catalyst for the one‐pot synthesis of spirooxindole‐dihydropyridines

Dong

Wang

Zhang

et al. 2022

Applied Organom Chemis

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Magnetic materials show promising applications in heterogeneous catalysis because of their ease of separation and good reusability. The present work reports the design, synthesis, and characterization of a novel magnetic biochar supported nickel catalyst. Fourier infrared spectroscopy (FT‐IR), powder X‐ray diffraction technology (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and vibrating sample magnetometer (VSM) techniques were used for analyzing the prepared catalyst. The prepared catalyst exhibited excellent catalytic activity for synthesis of spirooxindole‐dihydropyridines derivatives by a one‐pot three‐component reaction of isatin, barbituric acid, and 6‐amino uracil or 1H‐pyrazol‐5‐amine. This new methodology demonstrated some important features, including high yields, lower loading of the catalyst, easy work‐up, and recyclability of the catalyst for a minimum of six times without an obvious decay of catalytic performance.

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Section: Introductionmentioning

confidence: 99%

Nickel supported on magnetic biochar as a highly efficient and recyclable heterogeneous catalyst for the one‐pot synthesis of spirooxindole‐dihydropyridines

Dong

Wang

Zhang

et al. 2022

Applied Organom Chemis

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“…[2][3][4] The oxindole ring fused to the pyrrolidine system, namely, the spirooxindole pyrrolidines, requires special mention in heterocyclic chemistry owing to their compelling biological reliability (Scheme 2) since the last decade. [5][6][7][8][9][10] The anticancer, [5,6] antimalarial, [7] antileishmenic [8] and antiviral [9] properties of these heterocycles are well known with evaluated cytotoxic activity, [10] consequently inviting several synthetic approaches [11][12][13] to these biologically relevant synthons. Recently, the spirooxindole-pyrrolidine derivatives are identified to exhibit antimicrobial and acetylcholinesterase inhibitory activities.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

Acharjee

Mohammad‐Salim

Chakraborty

et al. 2021

J of Physical Organic Chem

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A molecular electron density theory (MEDT) study for the [3 + 2] cycloaddition (32CA) reaction of indoledione and N-methyl glycine with (E)-1-bromonitrostyrene leading to the spirooxindole-pyrrolidine adduct is presented. Electron localisation function (ELF) study of the in situ generated azomethine ylide classifies a pseudodiradical electronic structure associated with low activation energies. This 32CA reaction is a polar process with electronic flux from the strongly nucleophilic azomethine ylide to the strongly electrophilic nitrostyrene, confirmed from the global electron density transfer (GEDT) above 0.20 e at the transition states (TSs). Parr function analysis predicts the correct regioselectivity from the two-centre interactions. The reaction is kinetically controlled with negative free energy of reaction which makes it irreversible. The activation enthalpy of the favoured TS is lowered by 3.4, 6.3 and 9.3 kcal mol −1 in methanol relative to the other feasible reaction paths,

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“…In 2019, Tumskiy et al synthesized five spirooxindolepyrrolidines and examined the cytotoxic activity against some cell lines (Vero normal and HeLa cancer cells). The results demonstrated that hit III having a pyridine moiety with the chlorine atom in the ortho position exhibited a moderate selectivity (3-fold) between HeLa cancer cells and Vero healthy cells [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

et al. 2021

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A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC50 = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC50 = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO2 substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC50 = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.

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Synthesis of novel spirooxindole-pyrrolidines and evaluation of their cytotoxic activity

Cited by 17 publications

References 12 publications

Nickel supported on magnetic biochar as a highly efficient and recyclable heterogeneous catalyst for the one‐pot synthesis of spirooxindole‐dihydropyridines

Nickel supported on magnetic biochar as a highly efficient and recyclable heterogeneous catalyst for the one‐pot synthesis of spirooxindole‐dihydropyridines

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

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