Synthesis and structure–activity relationships of N-aryl(indol-3-yl)glyoxamides as antitumor agents

Marchand, Pascal; Antoine, Maud; Baut, G. Le; Czech, Michael P.; Baasner, Silke; Günther, E

doi:10.1016/j.bmc.2009.07.048

Cited by 16 publications

(9 citation statements)

References 32 publications

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“…Phenol 12 was converted to triflate 13 , which in the presence of a Pd catalyst and zinc cyanide was transformed into 14 [32]. Bromination of this material gave 15 [33] 7-Chloroindole ( 16 ) was converted to 17a and then to 17b [34]. The nitrile was subsequently reduced to aldehyde 17c , which was transformed to hydantoin 18 [15].…”

Section: Methodsmentioning

confidence: 99%

Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1

Maki¹,

Smith²,

Teng³

et al. 2012

Analytical Biochemistry

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Necrotic cell death is prevalent in many different pathologic disease states and in traumatic injury. Necroptosis is a form of necrosis that stems from specific signaling pathways with the key regulator being RIP1, a serine/threonine kinase. Specific inhibitors of RIP1, termed necrostatins, are potent inhibitors of necroptosis. Necrostatins are structurally distinct from one another yet still possess the ability to inhibit RIP1 kinase activity. To further understand the differences in the binding of the various necrostatins to RIP1 and to develop a robust HTS assay, which can be used to identify new classes of RIP1 inhibitors, we synthesized fluorescein-derivatives of Necrostatin-1 (Nec-1) and Necrostatin-3 (Nec-3). These compounds were used to establish a fluorescence polarization (FP) assay to directly measure the binding of necrostatins to RIP1 kinase. The fluorescein-labeled compounds are well suited for HTS since the assays have a DMSO tolerance up to 5% and Z' scores of 0.62 (fluorescein-Nec-1) and 0.57 (fluorescein-Nec-3). Additionally, results obtained from the FP assays and ligand docking studies provide insights into the putative binding sites of Nec-1, Nec-3, and Nec-4.

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Section: Methodsmentioning

confidence: 99%

Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1

Maki¹,

Smith²,

Teng³

et al. 2012

Analytical Biochemistry

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“…The possibility of choosing the substituents of the chain, always seeking a better interaction with biological targets, and possible modulation of the lipophilic character of new derivatives, make semicarbazone intermediates important for the design of drugs [22]. In this context, in continuation of the work of our research groups in the development of new antitumor agents [23][24][25][26][27][28][29][30], the present study aimed to synthesize arylsemicarbazone derivatives with the purpose of evaluating their anticancer activity and their inhibition of protein kinases. Although the synthesis of some of these compounds has already been described in the literature [22,[31][32][33], the study of anticancer activity is reported for the first time in this work.…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents

et al. 2019

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Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM).

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“…Unlike many anti-mitotic agents, it does not exert peripheral neuropathy; this benefit distinguishes indibulin from other similar acting compounds [14]. Significant efforts have been made to find new anti-tubulin derivatives, inspired by the structure of indibulin [15][16][17] (Figure 2). Indibulin ( Figure 2) is a new generation of anticancer compound with anti-mitotic properties.…”

Section: Introductionmentioning

confidence: 99%

2-[2-Methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide

Moghadam

Amini

2018

Molbank

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Synthesis and structure–activity relationships of N-aryl(indol-3-yl)glyoxamides as antitumor agents

Cited by 16 publications

References 32 publications

Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1

Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1

Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents

2-[2-Methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide

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