Design and synthesis of naphthoquinone derivatives as antiproliferative agents and 20S proteasome inhibitors

The 20S proteasome is a valuable target for the treatment of a number of diseases including cancer, neurodegenerative disease, and parasitic infection.

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Computer Modeling-Assisted Design And Synthesis Of Flavonols Derivatives As Proteasome Inhibitors

Planta Medica ◽

10.1055/s-0036-1578757 ◽

2016 ◽

Vol 82 (05) ◽

Author(s):

KY Orabi ◽

MS Abaza ◽

KA ElSayed ◽

AY Elnagar ◽

SI Faggal ◽

...

Keyword(s):

Computer Modeling ◽

Proteasome Inhibitors ◽

Design And Synthesis

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Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors

European Journal of Organic Chemistry ◽

10.1002/ejoc.201000317 ◽

2010 ◽

Vol 2010 (21) ◽

pp. 3991-4003 ◽

Cited By ~ 45

Author(s):

Jérôme Clerc ◽

Barbara Schellenberg ◽

Michael Groll ◽

André S. Bachmann ◽

Robert Huber ◽

...

Keyword(s):

Proteasome Inhibitors ◽

Biological Evaluation ◽

20S Proteasome ◽

Convergent Synthesis ◽

Synthesis And Biological Evaluation

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Design and Synthesis of New [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives as Potential Antiproliferative Agents

Bulletin of the Korean Chemical Society ◽

10.1002/bkcs.10363 ◽

2015 ◽

Vol 36 (7) ◽

pp. 1863-1873 ◽

Cited By ~ 3

Author(s):

Ahmed Elkamhawy ◽

Mohammad M. Al-Sanea ◽

Chiman Song ◽

Taebo Sim ◽

Eun Joo Roh

Keyword(s):

Pyrimidine Derivatives ◽

Antiproliferative Agents ◽

Design And Synthesis

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Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

Molecules ◽

10.3390/molecules26226798 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6798

Author(s):

Essmat M. El-Sheref ◽

Mohammed A. I. Elbastawesy ◽

Alan B. Brown ◽

Ahmed M. Shawky ◽

Hesham A. M. Gomaa ◽

...

Keyword(s):

Cell Cycle ◽

Click Reaction ◽

Annexin V ◽

Antiproliferative Agents ◽

Design And Synthesis ◽

Cycle Arrest ◽

M Phase ◽

Reaction Potential ◽

Apoptotic Activity ◽

Mcf 7

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC50 = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.

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Design, synthesis and biological evaluation of triaryl compounds as novel 20S proteasome inhibitors

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2020.127508 ◽

2020 ◽

Vol 30 (21) ◽

pp. 127508

Author(s):

Yajun Yang ◽

Ke Wang ◽

Bo Wu ◽

Ying Yang ◽

Fangfang Lai ◽

...

Keyword(s):

Proteasome Inhibitors ◽

Biological Evaluation ◽

20S Proteasome ◽

Design Synthesis ◽

Synthesis And Biological Evaluation

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Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2016.04.052 ◽

2016 ◽

Vol 118 ◽

pp. 230-243 ◽

Cited By ~ 29

Author(s):

Marcella Bassetto ◽

Salvatore Ferla ◽

Fabrizio Pertusati ◽

Sahar Kandil ◽

Andrew D. Westwell ◽

...

Keyword(s):

Prostate Cancer ◽

Antiproliferative Agents ◽

Design And Synthesis

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Sequence analysis of β-subunit genes of the 20S proteasome in patients with relapsed multiple myeloma treated with bortezomib or dexamethasone

Blood ◽

10.1182/blood-2012-05-426924 ◽

2012 ◽

Vol 120 (23) ◽

pp. 4513-4516 ◽

Cited By ~ 46

Author(s):

David I. Lichter ◽

Hadi Danaee ◽

Michael D. Pickard ◽

Olga Tayber ◽

Michael Sintchak ◽

...

Keyword(s):

Multiple Myeloma ◽

Single Nucleotide Polymorphism ◽

Proteasome Inhibitors ◽

Proteasome Inhibition ◽

Allelic Frequency ◽

High Dose ◽

20S Proteasome ◽

Clinical Relapse ◽

Nucleotide Polymorphism ◽

Single Nucleotide

AbstractVariations within proteasome β (PSMB) genes, which encode the β subunits of the 20S proteasome, may affect proteasome function, assembly, and/or binding of proteasome inhibitors. To investigate the potential association between PSMB gene variants and treatment-emergent resistance to bortezomib and/or long-term outcomes, in the present study, PSMB gene sequence variation was characterized in tumor DNA samples from patients who participated in the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib versus high-dose dexamethasone for treatment of relapsed multiple myeloma. Twelve new PSMB variants were identified. No associations were found between PSMB single nucleotide polymorphism genotype frequency and clinical response to bortezomib or dexamethasone treatment or between PSMB single nucleotide polymorphism allelic frequency and pooled overall survival or time to progression. Although specific PSMB5 variants have been identified previously in preclinical models of bortezomib resistance, these variants were not detected in patient tumor samples collected after clinical relapse from bortezomib, which suggests that alternative mechanisms underlie bortezomib insensitivity. This study is registered at www.clinicaltrials.gov as NCT00048230.

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