Botany - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/32
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Item Molecular docking and in vitro study of Syzygium cumini-derived natural compounds on receptor tyrosine kinases pathway components(Inderscience Enterprises Ltd., 2019) Singh, P; Bast, Felix; Bhushan, S; Mehra, R; Kamboj, P.Syzygium cumini (S. cumini) is used for a variety of biological activities such as anti-inflammatory, anti-diabetic and anti-oxidant; currently, it has been reported for DNA protecting activity against radiation damage. Receptor tyrosine kinases (RTKs) are identified as critical regulators of various cellular processes including cell proliferation, metabolism and apoptosis. These receptors have recently gained attention as an attractive target for cancer treatment. The present research was aimed to screen S. cumini-derived natural compounds against RTKs pathway components using molecular docking. Furthermore, in vitro anti-proliferative 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and anti-oxidative (nitro blue tetrazolium and H 2 CDFD) activities of leaf extract of S. cumini are also reported. Selected natural compounds were docked with X-ray crystal structure of RTKs signalling proteins using grid-based ligand docking with energetics Maestro 9.6. In the present investigation, our result highlighted that myricetin, kaempferol, delphinidin chloride, ellagic acid, rutin, petunidin, gossypol and mirtillin generated a good dock score with all selected proteins. Protein-ligand interactions accentuated that several bonds such as lipophilic, hydrogen bonding, π-π stacking and cation-π interactions represent a ruling contribution at the active site. Moreover, reduction in cell viability with leaf extract of S. cumini treatment at concentrations of 5-80 µg/ml after 48 h in MCF-7 cells was observed. Leaf extract of S. cumini significantly reduced the Reactive oxygen species (ROS) generation in MCF-7 cells after 48 h. These results indicate the anti-cancer potential of S. cumini. Thus, isolation and purification of anti-cancerous compounds are suggested to explore more possibilities in the field. © 2019 Inderscience Enterprises Ltd.Item In Silico and In Vitro Studies Evidenced Anticancer Natural Compounds, a Targeting Chemokine Receptor(iMedPub, 2016) Singh, Pushpendra; Bast, FelixChemokines 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.Item Screening of multi-targeted natural compounds for receptor tyrosine kinases inhibitors and biological evaluation on cancer cell lines, in silico and in vitro(Humana Press Inc., 2015) Singh, Pushpendra; Bast, FelixReceptors 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??M 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. ? 2015, Springer Science+Business Media New York.Item Natural Compounds Targeting Transforming Growth Factor-β: In Silico and In Vitro Study(ejBio, 2016) Singh, Pushpendra; Bast, Felix; Singh, Ravi ShankarInhibition of the tumor-promoting effects of transforming growth factor beta receptor (TGFβR) in carcinogenesis provides a better therapeutic intervention. Various natural compounds, inhibitors of TGFβR have been used for in vitro and in vivo anticancer study. Although very few TGFβR inhibitors are now intensifying in preclinical studies. In this study our aim to investigate TGFβR1, TGFβR2 and TAK1 inhibitor by using molecular docking and in vitro study. Our result revealed that some compounds have better docking energy. Moreover, the effect of two lead molecules epigallocatechin gallate (EGCG) and myricetin on the mRNA expression of TGFβR1 was reported after the 48 hrs treatments in HepG2 and PC3 cancer cell lines. The RT-PCR showed that compound EGCG and myricetin reduced the mRNA expression of TGFβR1 at 80 μM concentration. This molecular docking study provides a better understanding of binding of compounds to the active site of proteins and to summarize the various binding energy, hydrophobic, hydrogen, an electrostatic bond that are decisive for the protein-ligand interactions. Further experimental work will be required for validation of our results.