Synthesis of new thieno[2,3-<i>b</i>]pyridine derivatives as pim-1 inhibitors

Naguib, Bassem H.; El‐Nassan, Hala B.

doi:10.3109/14756366.2016.1158711

Cited by 27 publications

(11 citation statements)

References 30 publications

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“…The rest of the synthesized compounds displayed poor enzyme inhibitory activity. These results were far better than those obtained with thieno[2,3- b ]pyridine derivatives 24 .…”

Section: Resultsmentioning

confidence: 53%

“…In an attempt to prepare potent pim-1 inhibitors that can be used as anticancer agents, we had recently reported the pim-1 inhibitory activity of thieno[2,3- b ]pyridine derivatives V ( Figure 2 ) 24 as bioisosteres to benzofuran-2-carboxylic acids 25 . However, their pim-1 inhibitions as well as their cytotoxic activities were only moderate to poor.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of new pyridothienopyrimidinone derivatives as Pim-1 inhibitors

Naguib

El‐Nassan

Abdelghany

2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Four series of pyridothienopyrimidin-4-one derivatives were designed and prepared to improve the pim-1 inhibitory activity of the previously reported thieno[2,3-b]pyridines. Significant improvement in the pim-1 inhibition and cytotoxic activity was achieved using structure rigidification strategy via ring closure. Six compounds (6c, 7a, 7c, 7d, 8b and 9) showed highly potent pim-1 inhibitory activity with IC50 of 4.62, 1.18, 1.38, 1.97, 8.83 and 4.18 μM, respectively. Four other compounds (6b, 6d, 7b and 8a) showed moderate pim-1 inhibition. The most active compounds were tested for their cytotoxic activity on three cell lines [MCF7, HCT116 and PC3]. Compounds 7a [the 2-(2-chlorophenyl)-2,3-dihydro derivative] and 7d [the 2-(2-(trifluoromethyl)-phenyl)-2,3-dihydro derivative] displayed the most potent cytotoxic effect on the three cell lines tested consistent with their highest estimated pim-1 IC50 values.

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“…The rest of the synthesized compounds displayed poor enzyme inhibitory activity. These results were far better than those obtained with thieno[2,3- b ]pyridine derivatives 24 .…”

Section: Resultsmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Synthesis of new pyridothienopyrimidinone derivatives as Pim-1 inhibitors

Naguib

El‐Nassan

Abdelghany

2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Thieno[2,3- b ]pyridines are known to modulate the activity of numerous molecular targets, including G protein-coupled receptors [ 15 ], P2Y12 receptors [ 31 ], tyrosyl DNA phosphodiesterase 1–a DNA repair enzyme [ 32 ], the colchicine binding site of tubulin [ 33 ], phospholipase C-δ1 [ 21 ] as well as PIM-1 [ 34 ] and eukaryotic elongation factor-2 kinase [ 35 ], and cyclooxygenases [ 36 ]. It can therefore be stated that compound 1 is modulating many processes affecting E-selectin.…”

Section: Discussionmentioning

confidence: 99%

Thieno[2,3-b]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s+ Breast Cancer Cells

et al. 2021

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The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is a glycoconjugate sialyl Lewis x (CD15s), which may be expressed as an oligosaccharide branch of the CD44 glycoprotein, as well as a self-contained glycosphingolipid. It is also known that increased sialylation of glycoconjugates is a feature of malignant cells. The aim of the study was to analyse the effect of a novel thieno[2,3-b]pyridine, compound 1, in MDA-MB-231 triple-negative breast cancer cells (TNBCs) upon CD15s and CD44 expression in different cell subpopulations using flow cytometry. CD15s expression was compared between mesenchymal-like cancer stem cells (CSC, CD44+CD24−), epithelial cells without CD44 (CD44−CD24+ and CD44−CD24−), and CD44+CD24+ cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s+CSC and CD15s−CSC was determined. Compound 1 significantly decreased the percentage of CD15s+CSC, CD15s+CD44+CD24+, and CD15s+CD44− subpopulations, as well as the expression of CD15s in CD44+CD24+ and CD44− cells, and therefore shows potential as a treatment for TNBC.

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“…On the other hand, many reports have documented the important biological activities of thieno[2,3- b ]pyridine derivatives in anticancer [ 19 , 20 , 21 ], antimicrobial [ 22 , 23 ], antiviral [ 24 , 25 ], anti-inflammatory [ 26 ] and osteogenic [ 27 ] activities. As a result, thieno[2,3- b ]pyridine compounds and their fused derivatives with the bioactive pyrimidine ring [ 28 , 29 ] have attracted great interest in the last decade; several pyrido[3’,2’:4,5]thieno[3,2- d ]pyrimidine derivatives were synthesized and gave significant pharmacological properties as antimicrobial [ 30 , 31 , 32 ], anticancer [ 33 , 34 ] and protein kinase inhibitors [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors

et al. 2020

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The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,b–a,b) were synthesized by a series of various reactions, starting with 3-aminothieno[2,3-b]pyridine-2-carboxamides (1a,b). Condensation of compounds 1a,b with cyclohexanone gave 1’H-spiro[cyclohexane-1,2’-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin]-4’(3’H)-ones (2a,b), which in turn were utilized to afford the target 4-substituted derivatives (3a,b–8a,b). In vitro antibacterial activity evaluations of all the new compounds (2a,b–8a,b) were performed against six strains of Gram-negative and Gram-positive bacteria. The target compounds showed significant antibacterial activity, especially against Gram-negative strains. Moreover, the compounds (2a,b; 3a,b; 4a,b; and 5a,b) that exhibited potent activity against Escherichia coli were selected to screen their inhibitory activity against Escherichia coli topoisomerase II (DNA gyrase and topoisomerase IV) enzymes. Compounds 4a and 4b showed potent dual inhibition of the two enzymes with IC50 values of 3.44 µΜ and 5.77 µΜ against DNA gyrase and 14.46 µΜ and 14.89 µΜ against topoisomerase IV, respectively. In addition, docking studies were carried out to give insight into the binding mode of the tested compounds within the E. coli DNA gyrase B active site compared with novobiocin.

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Synthesis of new thieno[2,3-b]pyridine derivatives as pim-1 inhibitors

Cited by 27 publications

References 30 publications

Synthesis of new pyridothienopyrimidinone derivatives as Pim-1 inhibitors

Synthesis of new pyridothienopyrimidinone derivatives as Pim-1 inhibitors

Thieno[2,3-b]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s+ Breast Cancer Cells

Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors

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