New phosphazine and phosphazide derivatives as multifunctional ligands targeting acetylcholinesterase and β-Amyloid aggregation for treatment of Alzheimer's disease

El‐Sayed, Naglaa F.; El‐Hussieny, Marwa; Ewies, Ewies F.; Fouad, Marwa A.; Boulos, L. S.

doi:10.1016/j.bioorg.2019.103499

Cited by 14 publications

(7 citation statements)

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“…Accordingly, and in continuation of our ongoing research (Boulos et al, 2013a;El-Sayed et al, 2016;Ewies et al, 2014;Ewies et al, 2015;Ewies et al, 2016a;Ewies et al, 2016b;Ewies et al, 2019;Ibrahim et al, 2015, El-Husseiny et al, 2020El-Sayed et al, 2020) toward obtaining new compounds as promising biological activities and based on F I G U R E 2 Design of target compounds 5a-j, 6a,b, 7a-e, and 8a-f the previously reported findings regarding the biological activity of benzofuran and indole nucleus, we focused our attention on exploring the possibility of replacement of the 3,4,5-trimethoxybenzoyl moiety at position 2 of compound IV with a fluoro or trifluoromethyl substituted phenyl diazinyl moiety as in compounds 5a-j, 6a,b, and 8a-f. Both fluorine substituent or trifluoromethyl group are known to induce high effect on the binding affinity and increase stability of cell membrane as well as its permeability against metabolic oxidation (Usachev et al, 2008;Usachev et al, 2012).…”

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confidence: 71%

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors

El‐Sayed

El‐Hussieny

Ewies

et al. 2021

Drug Development Research

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Microtubules and the mitotic spindle have become an important target for cancer treatment due to their critical role in cell division. In this work, a novel series of benzofuran and indole derivatives were designed and synthesized, to be evaluated as tubulin polymerization inhibitors. 2‐Acetylbenzofuran derivatives 1a,b and 3‐acetylindole 1c were condensed with Wittig reagents 2a–d and Wittig‐Horner reagents 3a–e to afford the respective 2‐ethylidene derivatives 5a–j and 7a–e. Also, iminomethylene triphenylphosphine (2e) reacted with 1a,b to afford benzofuran‐2‐ylethylidene aniline derivatives 6a,b. In addition, compounds 1a,b reacted with trialkylphosphites 4a–c to give 1:1 adduct for which the Oxaphospholo[4,3‐b]benzofuran‐7‐yl)diazene derivatives 8a–f, were assigned. The possible reactions mechanisms were discussed and structural reasoning for the new compounds were based upon spectroscopic data. Their antiproliferative activities against two cell lines namely, HepG2 and MCF7 cells were then evaluated. It was found that the benzofuran compounds 5b, 6a, and 8c exhibited the strongest antiproliferative activities against both cell lines compared to doxorubicin. By studying the mechanism of action, compound 6a showed good inhibition of tubulin polymerization which leads to mitotic spindle formation disruption, cell cycle arrest in the G2/M phase, and apoptosis of HepG2 cells. A conducted docking study confirmed the in vitro results indicating that compound 6a fitted properly at the colchicine binding site of tubulin. Based on these findings, compound 6a can be considered as a promising anticancer candidate that can be subjected for further development as a tubulin polymerization inhibitor for treating liver and breast cell carcinoma.

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confidence: 71%

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors

El‐Sayed

El‐Hussieny

Ewies

et al. 2021

Drug Development Research

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“…Compounds in ( Figure 2 -(19,24,25,32 and 33)) that were reported to possess the most potential anticholinesterase activity [ 66 , 69 , 72 ] were selected to investigate their possible interactions with the binding pocket of the downloaded enzyme. The acetylcholinesterase active site consists mainly of three subsites; a peripheral anionic site (PAS) including Trp286, Tyr124, Asp74, and Phe295; and a mid-aromatic gorge and a catalytic active site (CAS) comprising Trp86, Glu202, Tyr337, and Gly448 residues [ 99 , 100 ]. As shown in Figure 5 a, the five compounds were successfully docked in the entire enzymatic gorge with high docking scores ranging from −19.58095 to −27.19648 kcal/mol, Supplementary Table S1 .…”

Section: Molecular Docking Study Of Selected Biologically Active Comp...mentioning

confidence: 99%

Unveiling Natural and Semisynthetic Acylated Flavonoids: Chemistry and Biological Actions in the Context of Molecular Docking

et al. 2022

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Acylated flavonoids are widely distributed natural metabolites in medicinal plants and foods with several health attributes. A large diversity of chemical structures of acylated flavonoids with interesting biological effects was reported from several plant species. Of these, 123 compounds with potential antimicrobial, antiparasitic, anti-inflammatory, anti-nociceptive, analgesic, and anti-complementary effects were selected from several databases including SCI-Finder, Scopus, Google Scholar, Science Direct, PubMed, and others. Some selected reported biologically active flavonoids were docked in the active binding sites of some natural enzymes, namely acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, aldose reductase, and HIV integrase, in an attempt to underline the key interactions that might be responsible for their biological activities.

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“…27,28 Moreover, several iminophosphoranes showed biological activity and were investigated as potential anticancer agents 29−32 and acetylcholinesterase (AChE) inhibitors targeting the treatment of Alzheimer's disease (Scheme 1b). 33 Conventionally, iminophosphoranes can be synthesized through Staudinger reduction 34−42 or by reacting phosphines with iminoiodanes (Scheme 2a,b). 43−46 Alternatively, Kirsanov, 47−52 Appel-type, 53−55 or Mitsunobu-type 56−62 reactions can be performed to generate an electrophilic phosphine intermediate in situ, which is then trapped by the nitrogen precursor (Scheme 2c−e).…”

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confidence: 99%

Efficient and Sustainable Electrosynthesis of N-Sulfonyl Iminophosphoranes by the Dehydrogenative P–N Coupling Reaction

Bieniek,

Nater,

Eberwein

et al. 2024

JACS Au

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Iminophosphoranes are commonly used reagents in organic synthesis and are, therefore, of great interest. An efficient and sustainable iodide-mediated electrochemical synthesis of Nsulfonyl iminophosphoranes from readily available phosphines and sulfonamides is reported. This method features low amounts of supporting electrolytes, inexpensive electrode materials, a simple galvanostatic setup, and high conversion rates. The broad applicability could be demonstrated by synthesizing 20 examples in yields up to 90%, having diverse functional groups including chiral moieties and biologically relevant species. Furthermore, electrolysis was performed on a 20 g scale and could be run in repetitive mode by recycling the electrolyte, which illustrates the suitability for large-scale production. A reaction mechanism involving electrochemical mediation by the iodide-based supporting electrolyte is proposed, completely agreeing with all of the results.

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New phosphazine and phosphazide derivatives as multifunctional ligands targeting acetylcholinesterase and β-Amyloid aggregation for treatment of Alzheimer's disease

Cited by 14 publications

References 74 publications

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors

Unveiling Natural and Semisynthetic Acylated Flavonoids: Chemistry and Biological Actions in the Context of Molecular Docking

Efficient and Sustainable Electrosynthesis of N-Sulfonyl Iminophosphoranes by the Dehydrogenative P–N Coupling Reaction

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