Multitargeted molecular docking study of plant-derived natural products on phosphoinositide-3 kinase pathway components

Singh, Pushpendra; Bast, Felix

doi:10.1007/s00044-013-0774-2

Cited by 24 publications

(11 citation statements)

References 51 publications

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“…Previously, other studies were carried out to predict the efficacy of PI3K inhibitors, but our results are not identical to theirs. This is more likely due to their use of different inhibitors and docking software (Sabbah, et al, 2010;Sabbah, et al, 2012;Singh and Bast, 2013;Kawade, et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

Chawsheen

Adham

2019

ARO

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The phosphatidylinositol 3-kinase (PI3K) family comprises lipid kinases that cross-link signals between living cells and their surroundings. PI3Ks are classified into several groups and isoforms with specific characteristics and functions. Genes encoding PI3Ks are mutated in several types of cancer, and their isoforms have varying capacity in promoting cell signaling and cancer progression. Many compounds have been introduced as PI3Kα inhibitors, but not all of them have the same inhibitory effects. For successful PI3K-related biomedical experiments, it is vital to select the most specific and potent compounds with the highest inhibitory effects for targeting this kinase. In this study, we investigate 28 well-recognized PI3Kα inhibitors through predicting their specificity and potency using the docking software AutoDock Vina. Our data showed that PF 05212384 had the highest docking score (−9.2 kcal/mol), and 3-methyladenine had the lowest docking score (−4.8 kcal/mol). Our data also showed different types of interactions and bonds formed between the inhibitors and protein residues. In conclusion, PF 05212384 and AZD 6482 compounds are the best candidates for targeting PI3Kα. In addition to hydrophobic interactions in the PI3Kα binding pocket, the formation of hydrogen bonds between these inhibitors and binding pocket residues was confirmed.

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Section: Resultsmentioning

confidence: 99%

Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

Chawsheen

Adham

2019

ARO

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“…Ligand molecules were selected in our study: (a) IBS natural compound library (InterBioScreen Ltd) and (b) anticancer natural compounds having anticancer activity are reported in published literature, but mechanism of action is still awaited [15][16][17][18][19][20]. These 68 anticancer natural compounds (Table 1) are reported in our previously published article [21,22]. Ligands were prepared by using LigPrep module of the Maestro 9.6 application.…”

Section: Selection Of Ligand and Protein Moleculesmentioning

confidence: 99%

“…In silico molecular docking protocol was adapted from our published literature [21][22][23][24]. Receptor-based molecular docking was conducted using GLIDE software from Schrö-dinger suite [25][26][27].…”

Section: Molecular Dockingmentioning

confidence: 99%

Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro

Singh

Bast

2015

Med Oncol

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Receptors for growth factors encompass within the superfamily of receptor tyrosine kinases and are known to regulate numerous biological processes including cellular growth, proliferation, metabolism, survival, cell differentiation and apoptosis. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer owing to the evidence suggesting their over-expression in cancer cells. Therefore, we studied receptor-based molecular docking of IR (PDB; 3ETA), IGF1R (PDB; 1K3A), EGFR (PDB; 1M17), VEGFIR (PDB; 3HNG), and VEGFIIR (PDB; 2OH4) against natural compounds. Further, in vitro investigation of the biological effect of lead molecules in an array of cancer cell lines was done. All selected natural compounds were docked with the X-ray crystal structure of selected protein by employing GLIDE (Grid-based Ligand Docking with Energetics) Maestro 9.6. InterBioScreen natural compounds docked with each selected protein molecules by using GLIDE high throughput virtual screening. On the basis of Gscore, we select 20 compounds along with 68 anticancer compounds for GLIDE extra precision molecular docking. It was discovered in this study that compound epigallocatechin gallate (EGCG) yielded magnificent Gscore with IGF1R (PDB; 1K3A) and VEGFIIR (PDB; 2OH4), and protein-ligand interactions are chart out. Effect of EGCG on biological activity such as mRNA expression of selected protein, cell proliferation, oxidative stress, and cell migration was reported after the 48 h treatments in cancer cell lines. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of IGF1R, VEGFIIR, and mTOR at 80 μM concentration. Moreover, EGCG significantly reduced cell proliferation and ROS generation after 48 h treatments. Our result also indicated a reduction in the potential for cell migration that might show in vivo anti-metastasis activity of EGCG.

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“…In silico molecular docking protocol adapted from our previous published literature with some modification [11][12][13][14][15] (Figure 1). The database of 200 Marine and natural compounds used in our molecular docking studies were derived from different medicinal plant extracts.…”

Section: Selection Of Ligands and Protein Moleculesmentioning

confidence: 99%

In Silico and In Vitro Studies Evidenced Anticancer Natural Compounds, a Targeting Chemokine Receptor

Singh¹,

Bast²

2016

Ann Clin Lab Res

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Chemokines are a family of small chemotactic cytokines, which play a significant role in lymphocyte homing to secondary lymphoid organs in addition to tumor growth and metastasis. Thus, inhibition of chemokine receptor caught attention for anticancer treatment strategy. We studied molecular docking of chemokines receptor CXCR2, CXCR4, and CCR5 against natural and marine compounds. All selected natural and marine compounds were docked with the X-ray crystal structure of CXCR2, CXCR4, and CCR5 retrieved from the PDB by using Maestro 9.6. Molecular docking was executed by the XP (extra precision) mode of GLIDE. On the basis of Gscore and protein-ligand interactions, top-ranking compounds were outlined. The docking study carried out to summarize the various Gscore, hydrophobic, electrostatic bond, hydrogen bond, π-cation and π-π interactions and oversee the protein-ligand interactions. Moreover, effect of Epigallocatechin-3-gallate (EGCG) on biological activity such as mRNA expression (CXCR2, CCR5, and Bid), cell proliferation, ROS, and cell-migration was reported after the 48 hrs treatments in MCF-7 cells. The RT-PCR densitometric bands analysis showed that compound EGCG reduced the mRNA expression of CXCR2, CCR5 and increased the Bid at 40 µM and 80 μM concentration. Moreover, EGCG significantly reduced cell proliferation, ROS generation and cell-migration after 48 hours treatments.

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Multitargeted molecular docking study of plant-derived natural products on phosphoinositide-3 kinase pathway components

Cited by 24 publications

References 51 publications

Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro

In Silico and In Vitro Studies Evidenced Anticancer Natural Compounds, a Targeting Chemokine Receptor

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