Ultrasound-assisted one-pot green synthesis of new N- substituted-5-arylidene-thiazolidine-2,4-dione-isoxazoline derivatives using NaCl/Oxone/Na3PO4 in aqueous media

Thari, Fatima Zahra; Tachallait, Hamza; Alaoui, Nour-Eddine El; Talha, Aicha; Arshad, Suhana; Álvarez, Eleuterio; Karrouchi, Khalid; Bougrin, Khalid

doi:10.1016/j.ultsonch.2020.105222

Cited by 42 publications

(16 citation statements)

References 61 publications

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“…However, we were curious whether it would be possible to carry out a one-pot aza-Michael/Knoevenagel tandem reaction using only DABCO as the catalyst. To the best of our knowledge, there are not many examples of one-pot N -functionalization/Knoevenagel condensation of thiazolidine-2,4-dione compounds in the literature . Thus, after attempting to optimize the stoichiometry of the reaction components, it was found that treating 1 equiv of thiazolidine-2,4-dione 7 , 5 equiv of benzyl acrylate 9 and 2 equiv of 4-chlorobenzaldehyde 27 with DABCO at 100 °C in DMF and stirring overnight afforded the desired difunctionalized thiazolidine-2,4-dione 28 in 49% yield (Table , entry 5).…”

Section: Resultsmentioning

confidence: 99%

Development of a DABCO-Succinic Acid Based Catalytic System for the Aza-Michael Addition and Aza-Michael/Knoevenagel Tandem Reaction of Thiazolidine-2,4-dione to Electron Deficient Alkenes

et al. 2021

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A DABCO catalyzed aza-Michael addition of thiazolidine-2,4-dione to a variety of electron deficient alkenes has been developed. Additionally, a DABCO/succinic acid salt system has been designed that allows for the one pot tandem aza-Michael/Knoevenagel reaction of thiazolidine-2,4-dione to give difunctionalized thiazolidine-2,4-dione products. To the best of our knowledge, this is the first example of a one-pot tandem aza-Michael/Knoevenagel reaction involving thiazolidine-2,4-dione.

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Section: Resultsmentioning

confidence: 99%

Development of a DABCO-Succinic Acid Based Catalytic System for the Aza-Michael Addition and Aza-Michael/Knoevenagel Tandem Reaction of Thiazolidine-2,4-dione to Electron Deficient Alkenes

et al. 2021

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“…It was obtained as a white powder, in 64% yield, mp = 98 °C (Lit. mp 40 = 101–103 °C), R f = 0.69 (ethylacetate/ n -hexane, 1:3). IR (KBr) υ (cm –1 ): 1733 (C=O), 1685 (C=O), 1607 (C=C), 1115 (C-N).…”

Section: Methodsmentioning

confidence: 99%

Harnessing ROS-Induced Oxidative Stress for Halting Colorectal Cancer via Thiazolidinedione-Based SOD Inhibitors

et al. 2022

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Based on the “canonical” view of reactive oxygen species’ (ROS) contribution to carcinogenesis, ROS induce oxidative stress and promote various tumor progression events. However, tumor cells also need to defend themselves against oxidative damage. This “heresy” was supported by several recent studies underlining the role of cellular antioxidant capacity in promoting metastasis and resistance to chemotherapy. Accordingly, harnessing the ROS-induced oxidative stress via selective suppression of the cancer antioxidant defense machinery has been launched as an innovative anticancer strategy. Within this approach, pharmacological inhibition of superoxide dismutases (SODs), the first-line defense antioxidant enzymes for cancer cells, selectively kills tumor cells and circumvents their acquired resistance. Various SOD inhibitors have been introduced, of which some were tolerated in clinical trials. However, the hit SOD inhibitors belong to diverse chemical classes and lack comprehensive structure–activity relationships (SAR). Herein, we probe the potential of newly synthesized benzylidene thiazolidinedione derivatives to inhibit SOD in colorectal cancer with special emphasis on their effects on correlated antioxidant enzymes aldehyde dehydrogenase 1 (ALDH1) and glutathione peroxidase (GPx). This may possibly bring a new dawn for utilizing thiazolidinediones (TZDs) in cancer therapy through SOD inhibition mechanisms. The preliminary 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all of the evaluated TZDs exhibited excellent safety profiles on normal human cells, recording an EC100 of up to 47.5-folds higher than that of doxorubicin. Compounds 3c , 6a , and 6e (IC50 = 4.4–4.7 μM) were superior to doxorubicin and other derivatives against Caco-2 colorectal cancer cells within their safe doses. The hit anticancer agents inhibited SOD (IC50 = 97.2–228.8 μM). Then, they were selected for further in-depth evaluation on the cellular level. The anticancer IC50 doses of 3c , 6a , and 6e diminished the antioxidant activities of SOD (by 29.7, 70.1, and 33.3%, respectively), ALDH1A (by 85.92, 95.84, and 86.48%, respectively), and GPX (by 50.17, 87.03, and 53.28%, respectively) in the treated Caco-2 cells, elevating the Caco-2 cellular content of ROS by 21.42, 7.863, and 8.986-folds, respectively. Docking simulations were conducted to display their possible binding modes and essential structural features. Also, their physicochemical parameters and pharmacokinetic profiles formulating drug-likeness were computed.

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“…To verify the effect of ultrasound irradiation on reaction success, a series of control experiments were conducted where sonification was exchanged for conventional mechanical magnetic stirring. In these cases, the reaction times were extended up to 12 h without full conversion [37] …”

Section: Substitution Reactionsmentioning

confidence: 99%

Thiazolidinediones: An In–Depth Study of Their Synthesis and Application to Medicinal Chemistry in the Treatment of Diabetes Mellitus

2021

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2,4‐Thiazolidinedione (TZD) is a privileged and highly utilised scaffold for the development of pharmaceutically active compounds. This sulfur‐containing heterocycle is a versatile pharmacophore that confers a diverse range of pharmacological activities. TZD has been shown to exhibit biological action towards a vast range of targets interesting to medicinal chemists. In this review, we attempt to provide insight into both the historical conventional and the use of novel methodologies to synthesise the TZD core framework. Further to this, synthetic procedures utilised to substitute the TZD molecule at the activated methylene C5 and N3 position are reviewed. Finally, research into developing clinical agents, which act as modulators of peroxisome proliferator‐activated receptors gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B) and aldose reductase 2 (ALR2), are discussed. These are the three most targeted receptors for the treatment of diabetes mellitus (DM).

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Ultrasound-assisted one-pot green synthesis of new N- substituted-5-arylidene-thiazolidine-2,4-dione-isoxazoline derivatives using NaCl/Oxone/Na3PO4 in aqueous media

Cited by 42 publications

References 61 publications

Development of a DABCO-Succinic Acid Based Catalytic System for the Aza-Michael Addition and Aza-Michael/Knoevenagel Tandem Reaction of Thiazolidine-2,4-dione to Electron Deficient Alkenes

Development of a DABCO-Succinic Acid Based Catalytic System for the Aza-Michael Addition and Aza-Michael/Knoevenagel Tandem Reaction of Thiazolidine-2,4-dione to Electron Deficient Alkenes

Harnessing ROS-Induced Oxidative Stress for Halting Colorectal Cancer via Thiazolidinedione-Based SOD Inhibitors

Thiazolidinediones: An In–Depth Study of Their Synthesis and Application to Medicinal Chemistry in the Treatment of Diabetes Mellitus

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