Molecular dynamic simulations and structure-based pharmacophore development for farnesyltransferase inhibitors discovery

Moorthy, N. S. Hari Narayana; Sousa, Sérgio F.; Ramos, María J.; Fernandes, Pedro A.

doi:10.3109/14756366.2016.1144593

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…The last 90 ns of the simulation were considered for hydrogen bonding analysis, and cluster analysis of the conformations was generated. This overall procedure has been previously used with success in the treatment of several biomolecular systems [49][50][51][52][53][54][55][56][57].…”

Section: Molecular Dynamics Simulations and Free Energy Calculationsmentioning

confidence: 99%

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights

et al. 2021

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A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

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Section: Molecular Dynamics Simulations and Free Energy Calculationsmentioning

confidence: 99%

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights

et al. 2021

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“…This overall procedure has been previously used with success in the treatment of several biomolecular systems. 51–59…”

Section: Methodsmentioning

confidence: 99%

Synthesis, computational and nanoencapsulation studies on eugenol-derived insecticides

et al. 2022

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“…FTIs are a kind of anticancer reagents targeting tumor cell signal transduction pathways [17,18]. They can inhibit the farnesylation of many proteins including Ras to exert the antitumor effect [1].…”

Section: Discussionmentioning

confidence: 99%

A farnesyl transferase inhibitor induces apoptosis of insulinoma pancreatic β cells of mouse

Gao¹,

Fu²,

Liu³

et al. 2018

biomedicalresearch

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This study is to investigate the effect of a Farnesyl Transferase Inhibitor (FTI) R115777 on apoptosis of mouse insulinoma pancreatic β cells. MTT assay was used to investigate the proliferative inhibition of in vitro cultured mouse insulinoma pancreatic β cell lines by a FTI R115777. The morphological changes of the cells were observed using a fluorescence microscope by staining with Hoechst 33258 and propidium iodide after the treatment with FTI R115777. The apoptosis rate of R115777-treated beta-TC-6 cells was detected by flow cytometry. The expressions of caspase-3 and caspase-9 of the R115777-treated beta-TC-6 cells were assayed by spectrophotometry. In addition, the sub-cellular distribution of cytochrome c and the expressions of Bax and Bcl-2 proteins were detected by Western blot. After the treatment with FTI R115777, the proliferation of the mouse insulinoma pancreatic β cell lines was significantly inhibited. Significant apoptosis was observed in the treated beta-TC-6 cells. The effect of R115777 on the apoptosis of beta-TC-6 cells showed time-and dose-dependent manners. The expressions of caspase-3, caspase-9 and Bax in the R115777-treated beta-TC-6 cells increased, while the expression of Bcl-2 decreased. The sub-cellular distribution of cytochrome-c changed, with reduced cytochrome-c in mitochondria and increased cytochrome-c in cytoplasm. FTI R115777 can inhibit the proliferation of mouse insulinoma pancreatic β cell lines, and might induce cell apoptosis through the mitochondrionmediated pathway. R115777 could be further studied as a potential antitumor drug.

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Molecular dynamic simulations and structure-based pharmacophore development for farnesyltransferase inhibitors discovery

Cited by 9 publications

References 43 publications

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights

Synthesis, computational and nanoencapsulation studies on eugenol-derived insecticides

A farnesyl transferase inhibitor induces apoptosis of insulinoma pancreatic β cells of mouse

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