Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists

El‐Zahabi, Mohamed Ayman; El‐Bendary, Eman R.; Bamanie, Faida H.; Radwan, Mohamed F.; Ghareib, Salah A.; Eissa, Ibrahim H.

doi:10.1016/j.bioorg.2019.103115

Cited by 53 publications

(37 citation statements)

References 43 publications

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“…Then, the atoms with incorrect valence were corrected using the Valence monitor option. Then, the energy of the DNA–Topo complex was minimized by applying CHARMM and MMFF94 force fields as described in the Supporting Information . The active binding site from the receptor cavity was defined and prepared for docking procedure as described in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

Eissa

Metwaly

Belal

et al. 2019

Archiv der Pharmazie

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In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G-2, Hep-2, and Caco-2). Compounds 18b, 19b, 23, 25b, and 26 showed strong potencies against all tested cell lines with IC 50 values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC 50 values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities.Compounds 19b and 19c exhibited high activities against Topo II (IC 50 = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC 50 value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell-cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G-2 cells. It has revealed cell-cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl-2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA-Topo II complex to examine the binding patterns of the synthesized compounds. K E Y W O R D Santicancer, apoptosis, DNA intercalator, molecular docking, quinoxalines, topoisomerase II

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Section: Methodsmentioning

confidence: 99%

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

Eissa

Metwaly

Belal

et al. 2019

Archiv der Pharmazie

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“…The output from of MOE was further analyzed and visualized using Discovery Studio 4.0 soware. [58][59][60][61]…”

Section: Docking Studiesmentioning

confidence: 99%

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

et al. 2020

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“…Depending on ligand-based drug design approach, [56][57][58][59][60][61] it was determined to select compounds, some reported as DHFR inhibitors (I, II, III, IV, V, and VI), as lead compounds. I, III, IV, V, and VI), as lead compounds.…”

Section: Rationale Of Molecular Designmentioning

confidence: 99%

Synthesis and antitumor activity of some nitrogen heterocycles bearing pyrimidine moiety

Ahmed

El‐Hashash

Marzouk

et al. 2020

Journal of Heterocyclic Chem

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Synthesis of novel pyrimidine derivatives 4‐16 was accomplished by heterocyclization of polarized system, for example, Chalcone. Claisen‐Schmidt condensation of 2‐acetyl naphthalene with 4‐(N, N‐dimethylaminobenzaldehyde) afforded chalcone 3, which was utilized for synthesis various pyrimidine derivatives by treatment with urea, thiourea, and guandine hydrochloride in ethanolic sodium hydroxide solution. The reactivity of the synthesized pyrimidine derivatives towards different nucleophilic and electrophilic reagent were examined. The constructions of the newly synthesized pyrimidine derivatives were elucidated from their spectral and elemental analysis. All the synthesized compounds were tested in vitro for their anticancer activities against HePG‐2 and MCF‐7 cell lines. Some of them posses a wide range of pharmacological activity. Finally, a molecular docking study was conducted to reveal the probable interaction with the dihydrofolate reductase (DHFR) active site.

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Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists

Cited by 53 publications

References 43 publications

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

Synthesis and antitumor activity of some nitrogen heterocycles bearing pyrimidine moiety

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