Syntheses and antiproliferative evaluation of oxyphenisatin derivatives

Uddin, Muhammed K.; Reignier, Serge; Coulter, Tom; Montalbetti, Christian; Grånäs, Charlotta; Butcher, Steven P.; Krog-Jensen, Christian; Felding, Jakob

doi:10.1016/j.bmcl.2007.02.060

Cited by 84 publications

(68 citation statements)

References 16 publications

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“…We here demonstrate that two compounds TOP001 and the optimized analogue TOP216, belonging to a novel compound group based on a 1,3-dihydroindole-2-one scaffold, strongly inhibit the proliferation of cancer cells lines with striking selectivity (>1000 fold) against cancer cell lines that are insensitive to the compounds (18). In vivo, TOP001 and TOP216 show potent anti-cancer activity by inducing tumor regression (including cures) in mouse xenograft models of human tumours.…”

Section: Introductionmentioning

confidence: 82%

“…TOP001 and the chemically optimized analogues TOP216 and TOP385 are structurally related members of a compound series with remarkable anti-cancer properties (18). However the mechanism of action by which this novel compound class mediates these strong anti-cancer and anti-proliferative effects is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…TOP001, TOP216 and TOP385 were synthesized as previously described (18) Antibodies: phospho ACC(ser79), PathScan™ Multiplex Western Cocktail I: Phospho-p90RSK, Phospho-Akt, Phospho-p44/ 42 MAPK and Phospho-S6 Ribosomal, S6 ribosomal protein, S6 total protein; phospho p70 S6K (Thr389), phospho-eIF2 , eIF2 , phospho-GCN2 (Thr898), GCN2…”

Section: Reagents and Compoundsmentioning

confidence: 99%

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Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

Trojel-Hansen

Erichsen²,

Christensen³

et al. 2010

Cancer Chemother Pharmacol

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Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Reagents and Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

Trojel-Hansen

Erichsen²,

Christensen³

et al. 2010

Cancer Chemother Pharmacol

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“…(21)). Uddin et al demonstrated that the compound and its derivatives were potent antiproliferatives, particularly against the MDA-MB-468 cell line [154] (IC 50 value of oxyphenisatin (69) is 112 nM). The two hydroxyl groups on 69 are essential for activity and cytotoxicity can be increased (to less than 10 nM) by replacing small and lipophilic substituents in the 6-and/or 7-position of the isatin moiety.…”

Section: Fig (21)mentioning

confidence: 99%

“…The two hydroxyl groups on 69 are essential for activity and cytotoxicity can be increased (to less than 10 nM) by replacing small and lipophilic substituents in the 6-and/or 7-position of the isatin moiety. The lead analogue was the 6,7-difluorooxyphenisatin which displayed an IC 50 of 3 nM against MDA-MB-468 cells [154].…”

Section: Fig (21)mentioning

confidence: 99%

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Vine¹,

Matesic²,

Locke³

et al. 2013

Advances in Anticancer Agents in Medicinal Chemistry

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Isatin (1H-indole-2,3-dione) and its derivatives are responsible for a broad spectrum of biological activities. Among these the cytotoxic and antineoplastic properties have been the most widely reported. The synthetic versatility of the isatin, due to its privileged scaffold, has led to the generation of a large number of structurally diverse derivatives which include analogues derived from either mono-, di-, and trisubstitution of the aryl ring A, and/or those obtained by derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. These compounds inhibit cancer cell proliferation and tumour growth via interaction with a variety of intracellular targets such as DNA, telomerase, tubulin, P-glycoprotein, protein kinases and phosphatases. Herein we review recent highlights in the development of isatin-based compounds as anticancer agents with a particular focus on the cytotoxicity and structure activity relationships. Abstract:Isatin (1H-indole-2,3-dione) and its derivatives are responsible for a broad spectrum of biological activities. Among these the cytotoxic and antineoplastic properties have been the most widely reported. The synthetic versatility of the isatin, due to its privileged scaffold, has led to the generation of a large number of structurally diverse derivatives which include analogues derived from either mono-, di-, and tri-substitution of the aryl ring A, and/or those obtained by derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. These compounds inhibit cancer cell proliferation and tumour growth via interaction with a variety of intracellular targets such as DNA, telomerase, tubulin, Pglycoprotein, protein kinases and phosphatases. Herein we review recent highlights in the development of isatin-based compounds as anticancer agents with a particular focus on the cytotoxicity and structure activity relationships.

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Synthesis of 3,3‐Disubstituted Oxindoles Containing a 3‐(4‐Aminobut‐2‐ynyl) Unit via Domino Heck–Sonogashira Reaction in Water

Wang

Hao

et al. 2016

Adv Synth Catal

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In this study,p alladium-catalyzed domino Heck-Sonogashira reactions have been developed in water. Using this strategy, as erieso f3 -(4-aminobut-2-ynyl)oxindole derivatives with an all-carbon quaternary centera tt he 3-position were easily synthesized. Ther eactions provided products in excellent yieldsw ith ab road substrate tolerance.T he target product was readilyc onverted into apharmaceutically active molecule,w hich is used as a5 -HT 7 receptor antagonist.

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Syntheses and antiproliferative evaluation of oxyphenisatin derivatives

Cited by 84 publications

References 16 publications

Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

Recent Highlights in the Development of Isatin-Based Anticancer Agents

Synthesis of 3,3‐Disubstituted Oxindoles Containing a 3‐(4‐Aminobut‐2‐ynyl) Unit via Domino Heck–Sonogashira Reaction in Water

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