[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines

Mahboobi, Siavosh; Sellmer, Andreas; Höcher, Heymo; Eichhorn, Emerich; Bär, Thomas; Schmidt, Mathias; Maier, Thomas; Stadlwieser, Josef; Beckers, Thomas

doi:10.1021/jm060545p

Cited by 25 publications

(12 citation statements)

References 19 publications

(33 reference statements)

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“…4, 5). RKOp27 cells kip1 (25) have successfully been used to investigate cell cycle -dependent cytotoxicity of known and investigative chemotherapeutic agents (27,28). Induction of p27 kip1 arrests proliferating RKO cells in the G 1 phase of the cell division cycle, thereby inducing complete resistance to antimitotic agents like paclitaxel.…”

Section: Interference With Plk1 Function In Rkop27 Human Colon Adenocmentioning

confidence: 99%

Cell type–dependent effects of Polo-like kinase 1 inhibition compared with targeted polo box interference in cancer cell lines

Fink¹,

Sanders²,

Rippl³

et al. 2007

Molecular Cancer Therapeutics

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Multiple critical roles within mitosis have been assigned to Polo-like kinase 1 (Plk1), making it an attractive candidate for mitotic targeting of cancer cells. Plk1 contains two domains amenable for targeted interference: a kinase domain responsible for the enzymatic function and a polo box domain necessary for substrate recognition and subcellular localization. Here, we compare two approaches for targeted interference with Plk1

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Section: Interference With Plk1 Function In Rkop27 Human Colon Adenocmentioning

confidence: 99%

Cell type–dependent effects of Polo-like kinase 1 inhibition compared with targeted polo box interference in cancer cell lines

Fink¹,

Sanders²,

Rippl³

et al. 2007

Molecular Cancer Therapeutics

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“…Several protocols for the synthesis of 4-thiazolidinones are available in the literature [ 24 , 25 , 26 ]. Here 2-chloro- N -(2-chloro-5-nitrophenyl)acetamide ( 2a ), N -(4-acetylphenyl)-2-chloroacetamide ( 2b ), 2-chloro- N -(benzothiazol-2-yl)acetamide ( 2c ) and ethyl-4-(2-chloroacetamido)benzoate ( 2d ) were synthesized using a procedure reported earlier [ 25 ] starting from 2-chloro-5-nitroaniline ( 1a ), 4-amino acetophenone ( 1b ), 2-aminobenzothiazole ( 1c ) and benzocaine ( 1d ), respectively, upon heterocyclization of 2a–d in the presence of ammonium thiocyanate in refluxing ethanol, efficiently produced 2-(2-chloro-5-nitrophenyl-2-ylimino)thiazolidin-4-one ( 3a ), 2-(4-acetylphenylimino)thiazol- idin-4-one ( 3b ), 2-(benzothiazol-2-ylimino)thiazolidin-4-one ( 3c ) and ethyl-4-(4-oxothiazolidin-2-ylideneamino)benzoate ( 3d ), through intramolecular cyclization and the Dimroth-like rearrangements [ 27 ] (cf.…”

Section: Resultsmentioning

confidence: 99%

4-Thiazolidinones in Heterocyclic Synthesis: Synthesis of Novel Enaminones, Azolopyrimidines and 2-Arylimino-5-arylidene-4-thiazolidinones

Behbehani

Ibrahim

2012

Molecules

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The 4-thiazolidinones 3a–d were used as a key intermediates for the synthesis of 2-arylimino-5-arylidene-4-thiazolidinones derivatives 7a–p via nucleophilic addition reactions with the arylidene malononitrile. Moreover the 4-thiazolidinones 3a and 3c condensed with the DMF-DMA to form the corresponding enamines 8 and 9 depending on the reaction conditions. Otherwise the 4-thiazolidinone 3b reacts regioselectively with DMF-DMA to afford the enaminones 10 and 11, respectively. The latter reacts with many heterocyclic amines affording polyfunctionally substituted fused pyrimidine derivatives 13–18. The enamine 8b was also reacted with the 3-amino-1,2,4-triazole to afford the acyclic product 19, which could not be further cyclized to the corresponding tricyclic system 20. Moreover the 4-thiazolidinone 3c reacted with the benzenediazonium chloride to afford the arylhydrazones 12. The X-ray single crystal technique was employed in this study for structure elucidation and Z/E potential isomerism configuration determination. The X-ray crystallographic analyses of eight products could be obtained, thus establishing with certainty the structures proposed in this work.

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“…Inducible expression of p27Kip1 results in a complete cell cycle arrest in the G1 phase 24 hr after induction with ponasterone A. This system has been successfully used to determine cell cycle‐dependent cytotoxicity of known and investigational chemotherapeutic agents 20, 21. The results are shown in Figure 1 a .…”

Section: Resultsmentioning

confidence: 99%

Cell cycle‐dependent cytotoxicity and mitotic spindle checkpoint dependency of investigational and approved antimitotic agents

Birk

Bürkle

Pekari

et al. 2011

Intl Journal of Cancer

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The mitotic spindle checkpoint (SPC) is a highly regulated mechanism in eukaryotic cells that ensures the even distribution of the duplicated genome between daughter cells. Malfunction of the SPC or deregulated expression of SPC regulatory proteins is frequently associated with a poor response to chemotherapeutic agents. We investigated various approved and investigational mitosis‐specific agents, including spindle poisons, an Eg5 kinesin inhibitor, inhibitors of polo‐like kinase 1 (Plk1) or Aurora‐B kinase, a benzamide class HDAC inhibitor and compounds identified in a chemical genetics screen for their cell cycle‐dependent cytotoxicities and for their activities toward SPC deficient (HT29, Caco‐2, T47D) and SPC proficient human cell lines (A2780, HCT116, SW480). Using the RKOp27 cell system that allows inducible cell cycle arrest by the tunable expression of the cdk inhibitor p27Kip1, we found an exquisite proliferation‐dependent cytotoxicity for all compounds except the aurora kinase inhibitor VX‐680. Cytotoxicity of the antimitotic compounds was in general higher on SPC proficient than on deficient cells. We found two exceptions, a benzamide HDAC inhibitor which was effective on SPC proficient and deficient cells and an investigational compound, BYK72767, with a yet unknown mode of action. The degree of increased mitotic index was no predictor of cytotoxicity of the compounds nor was the phosphorylation of BubR1. However, SPC deficient cell lines were able to tolerate mitotic arrest for far longer times than SPC proficient cells. We conclude that targeting of SPC deficient cancers with novel antimitotic principles remains a challenge but certain drug classes may be equally efficacious regardless of SPC status.

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[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines

Cited by 25 publications

References 19 publications

Cell type–dependent effects of Polo-like kinase 1 inhibition compared with targeted polo box interference in cancer cell lines

Cell type–dependent effects of Polo-like kinase 1 inhibition compared with targeted polo box interference in cancer cell lines

4-Thiazolidinones in Heterocyclic Synthesis: Synthesis of Novel Enaminones, Azolopyrimidines and 2-Arylimino-5-arylidene-4-thiazolidinones

Cell cycle‐dependent cytotoxicity and mitotic spindle checkpoint dependency of investigational and approved antimitotic agents

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