Exploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic α-helix mimetics

Lim, Zelong; Duggan, Peter J.; Wan, Soo San; Lessène, Guillaume; Meyer, Adam G.; Tuck, Kellie L.

doi:10.1016/j.tet.2015.12.044

Cited by 8 publications

(6 citation statements)

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“…The Biginelli reaction [ 27 , 28 , 29 ] is an important MCR [ 30 ] because the products exhibit a wide range of biological activities. An acid-catalyzed Biginelli reaction involving a one-pot three component condensation of furochromone carbaldehyde ( 1 ), Curcumin ( 2 ), and urea/thiourea gave compounds 8a , b ( Scheme 5 ).…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

et al. 2018

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Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde (1) with Curcumin (2) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5H-furo [3, 2-g] chromen-5-one derivatives 4a–d, 6a–d, 7, 8a–d, 9 and 10 were synthesized by the reactions of furochromone carbaldehyde (1) with different reagents (namely: appropriate amine 3a–d, appropriate hydrazine 5a–d, hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate). The structure of the synthesized products had been confirmed from their spectroscopic data (IR, 1H-NMR, 13C-NMR and mass spectra). In the present investigation, the newly synthesized products were screened using the MTT colorimetric assay for their in vitro inhibition capacity in two human cancer cell lines (hepatocellular carcinoma (HEPG2) and breast cancer (MCF-7) as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-flurouracil and doxorubicin. The anticancer activity results indicated that the synthesized products 4c and 8b showed growth inhibition activity against HEPG2 cell line and synthesized products 4b and 8a showed growth inhibition activity against MCF-7, but with varying intensities in comparison to the known anticancer drugs, 5-flurouracil and doxorubicin. Cyclin dependent kinase 2 (CDK2), a major cell cycle protein, was identified as a potential molecular target of Curcumin. Furthermore, Curcumin induced G1 cell cycle arrest, which is regulated by CDK2 in cancer cells. Therefore, we used molecular modelling to study in silico the possible inhibitory effect of CDK2 by Curcumin derivatives as a possible mechanism of these compounds as anticancer agents. The molecular docking study revealed that compounds 4b, 8a and 8b were the most effective compounds in inhibiting CDk2, and, this result was in agreement with cytotoxicity assay.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

et al. 2018

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“…This new heterogeneous catalyst 10 was tested over five different reactions that require acid catalysis and that had advantageously already been catalyzed by parent imide 1 . More precisely catalyst 10 was used in a Ritter reaction (Scheme ; Table , entry 1), a Strecker reaction (Scheme ; Table , entry 2), a Fischer esterification (Scheme ; Table , entry 3), a Mannich reaction (Scheme ; Table , entry 4) and a Biginelli reaction (Scheme ; Table , entry 5). Results were generally excellent and very similar to those obtained using 1 as catalyst.…”

Section: Resultsmentioning

confidence: 99%

Silica Gel-Immobilized 1,2-Benzenedisulfonimide: A New and Versatile Brønsted Acid Heterogeneous Catalyst

et al. 2017

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a derivative of 1,2-benzenedisulfonimide, a strong and versatile Brønsted acid catalyst, has been immobilized on 3-aminopropil silica gel, by means of an amide bond, to afford a new heterogeneous catalyst. Its structure has been confirmed using IR and NMR spectroscopy. This new catalyst has been employed in five different organic reactions giving excellent results. At the end of the processes, it was recovered by easy filtration and reused without loss in its catalytic activity.

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“…The heterocyclic compounds containing pyrazole rings [38] (Scheme 3) were obtained via the condensation reaction of hydrazine derivatives(namely: hydrazine hydrate, phenyl hydrazine 4nitrophenyl hydrazine and 2,4-nitrophenyl hydrazine) with furochromone carbaldehyde a and curcumin b in the presence of ethanol/TEA for an appropriate time. [39] Isoxazole curcumin derivatives [40] were synthesized by the mechanical method instead of traditional heating which take a long time. In the agate mortar, acetic acid is a catalyst, and the curcuminoids grinding 1-2 mins is replaced with a hydroxylamine hydrochloride, and is an isoxazole curcumin derivative (Scheme 4).…”

Section: Synthesis Of β-Diketone Cyclic Curcumin Derivativesmentioning

confidence: 99%

“…This study made important discoveries and paved the way for further exploration in the design and development of more effective compounds for the treatment of head and neck cancers. Pyrazole thiazole compounds (33)(34)(35)(36)(37)(38)(39)(40) synthesized based on curcumin were screened by MTT test on the antiproliferative activities of COLO205, MCF-7, HepG2, A549, HeLa and HEK293 cells (Table 3). The anticancer potential of compound (33)(34)(35)(36)(37)(38)(39)(40) showed excellent to moderate activity on the growth of the tested cell lines.…”

Section: Modification Of Aromatic Heterocycles On Pyrazole Ringsmentioning

confidence: 99%

“…Pyrazole thiazole compounds (33)(34)(35)(36)(37)(38)(39)(40) synthesized based on curcumin were screened by MTT test on the antiproliferative activities of COLO205, MCF-7, HepG2, A549, HeLa and HEK293 cells (Table 3). The anticancer potential of compound (33)(34)(35)(36)(37)(38)(39)(40) showed excellent to moderate activity on the growth of the tested cell lines. Some synthetic compounds have shown varying degrees of anticancer activity.…”

Section: Modification Of Aromatic Heterocycles On Pyrazole Ringsmentioning

confidence: 99%

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Advances in β‐Diketocyclisation of Curcumin Derivatives and their Antitumor Activity

Dai,

Zhang,

Zheng

et al. 2024

Chemistry & Biodiversity

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Curcumin, derived from the popular spice turmeric, is a pharmacologically active polyphenol. Curcumin's therapeutic activity has been extensively studied in recent decades, with reports implicating curcumin in many biological activities, particularly, its significant anticancer activity. However, its potential as an oral administration product is hampered by poor bioavailability, which is associated with a variety of factors, including low water solubility, poor intestinal permeability, instability, and degradation at alkaline pH. To improve its bioavailability, modifying β‐diketone curcumin with heterocycles, such as pyrazole, isoxazole and triazole is a powerful strategy. Derivatives are synthesized while maintaining the basic skeleton of curcumin. The β‐diketone cyclized curcumin derivatives are regulators of multiple molecular targets, which play vital roles in a variety of cellular pathways. In some literatures, structurally modified curcumin derivatives have been compared with curcumin, and the former has enhanced biological activity, improved water solubility and stability. Therefore, the scope of this review is to report the most recently synthesized heterocyclic derivatives and to classify them according to their chemical structures. Several of the most important and effective compounds are reviewed by introducing different active groups into the β‐diketone position to achieve better therapeutic efficacy and bioavailability.

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Exploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic α-helix mimetics

Cited by 8 publications

References 47 publications

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

Design, Synthesis, Anticancer Evaluation and Docking Studies of Novel Heterocyclic Derivatives Obtained via Reactions Involving Curcumin

Silica Gel-Immobilized 1,2-Benzenedisulfonimide: A New and Versatile Brønsted Acid Heterogeneous Catalyst

Advances in β‐Diketocyclisation of Curcumin Derivatives and their Antitumor Activity

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