School Of Basic And Applied Sciences

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Author: search.filters.author.Singh, Pushpendra

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    Flavonols as cancer preventive agents: Recent updates
    (Nova Science Publishers, Inc., 2021-06-20T00:00:00) Kumar, Shashank; Singh, Pushpendra
    This book describes primary results on the leading edge of in silico and in vitro cancer research and summarizes the anticancer activity of pharmacologically important flavonols such as quercetin, morin, kaempferol, fisetin, galangin, diosmetin, and cianidanol. Natural products are a prime source of lead compounds suitable for further modification during drug development. Cancer drug discovery is a risky, costly, and resource-consuming process. In the modern arena, molecular computer modeling in anticancer drug development is utilized to speed up hit identification and optimization of the pharmacological profile. The first chapter of this book deals with computer-aided drug discovery and anticancer drug design using pharmacological active flavonols. In further chapters, the authors discuss the in vitro and in vivo advancement in anticancer research on important flavonols such as quercetin, morin, kaempferol, fisetin, galangin, diosmetin, and cianidanol. Anticancer advancement research related to various cancers is summarized and discussed, giving special emphasis on the effect on apoptosis, migrations, and growth via various signaling pathways. The book encompasses the literature as well as target identification for the selected flavonols for their in silico anticancer potential. Moreover, it also contains experimentation results and discussion on the pharmacological properties, including ADME/T, of the flavonols. Overall, this book can lay a good basis for the subsequent rise for its application as a therapeutic drug in the near future. � 2021 by Nova Science Publishers, Inc. All rights reserved.
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    Insilco Molecular Docking Study of Natural Compounds On Wild and Mutated Epidermal Growth Factor Receptor
    (Springer, 2014) Singh, Pushpendra; Bast, Felix
    The role played by overexpression of tyrosine kinase epidermal growth factor receptor (EGFR), the transmembrane receptor central to numerous cellular processes comprising cell migration, adhesion, apoptosis, and cell proliferation, has been highlighted in various cancers such as prostate, breast, lung, and ovarian cancers as well as in mutations in the EGFR kinase domain. Although many therapeutic approaches have targetted EGFR, the mutations occurring in the EGFR kinase domain including L858 EGFR and T790/L858R had led to the amplification of EGFR signals, consequently leading to increased cell proliferation and cell growth. The strategies involving the inhibition of EGFR L858 and T790M have been accredited with limited achievement in addition to being associated with unwanted adverse effects as a result of crosstalk of wild-type EGFR. All current EGFR tyrosine kinase inhibitors have been identified as ATP competitive inhibitors of wild-type EGFR possessing aniline and quinazoline moiety on the ligands skeleton. Our results obtained by performing molecular docking study on Maestro 9.3 molecular docking suite indicated that CID5280343 possesses better energy conformation against wild-type EGFR as well as two mutated EGFR. Moreover, it was discovered in this study that the natural compounds CID72276, CID5280445, CID441794, and CID72277 and InterBioScreen's library STOCK1N-78657, STOCK1N-78976, and STOCK1N-78847 have better binding conformation against gatekeeper T790M mutated EGFR concluded to be brought about by means of flexible ligands/receptor-based molecular docking protocol. Miraculous features of these compounds are their various pharmacokinetic and pharmacodynamic parameters which were found to be satisfactory as drug-like molecules. This molecular docking study also summarizes docking free energy, protein-ligands interaction profile, and pharmacokinetic and pharmacodynamic parameter of lead molecules which were tremendously helpful in enhancing the activity of these natural compounds against EGFR.
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    To study the effects of insulin and metformin on pc-3 cell line
    (Central University of Punjab, 2016) Singh, Pushpendra; Bast, Felix
    Dietary habits, genetic factors, hormonal factors and environmental factors are the independent risk factors for prostate cancer as well as diabetes. Androgen is the primary growth factor for the prostate cancer initiation and progression, however, non androgen peptide growth factor like insulin and insulin growth factor also involved in the prostate cancer as well as diabetes. Insulin and insulin growth factor are peptide that regulates metabolism, growth, cellular proliferation and apoptosis. The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent that improves insulin homeostasis and decreased growth and cellular proliferation of the prostate cancer cell line. Thus it is necessary to understand the growth promoting role of insulin on prostate cancer cell line and the possible influences of metformin on the proliferation of prostate cancer cell line in the presence and absence of insulin has been studied.
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    Natural Compounds Are Smart Players in Context to Anticancer Potential of Receptor Tyrosine Kinases: An In Silico and In Vitro Advancement
    (Springer, 2017) Singh, Pushpendra; Kumar, Shashank; Bast, Felix
    Cancer is the ruling cause of mortality worldwide. Chemotherapeutic toxicity and drug resistance have provided impulsion for the formulation of new anticancer agents. Receptor tyrosine kinases (RTKs) are the most activated cell surface receptors for copious polypeptide growth factors, cytokines, and hormones that play a considerable role in cancer initiation, promotion, and progression. Natural products are a prime source of new anticancer drugs and their leads. The objective of computer-aided drug design (CADD) is to enhance the set of compounds with prudent active drug-like properties and eliminate inactive, toxic, poor absorption, distribution, metabolism, and excretion toxicity (ADME/T) compounds. In the present chapter, in silico advancement of anticancer natural compounds and molecular mechanisms of action of flavonoids, viz., genistein, myricetin, quercetin, luteolin, morin, kaempferol, catechin, and epigallocatechin gallate (EGCG), on RTK and PI3K signaling pathway attributing to their potential anticancer activity have been discussed.
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    Homology modeling of chemokine CCR7, molecular docking, and in vitro studies evidenced plausible immunotherapeutic anticancer natural compounds
    (Birkhauser Boston, 2016) Singh, Pushpendra; Singh, Ravi Shankar; Rani, Alka; Bast, Felix
    The chemokine receptor 7 is a G-protein coupled, receptors coordinates the migration of cancer cells towards CCL19 and CCL21 constitutively expressed lymphatic organs. Chemokine receptor 7 facilitates cancer progression by generating new lymphatic vessels that serve as conduits for tumor dissemination to lymph nodes. In this context, chemokine receptor 7 inhibitor recently caught an attention for cancer cell growth inhibitor. The 3-D crystalline structure of chemokine receptor 7 not available in protein data bank (PDB), first we predicted the 3-D structure of chemokine receptor 7 and then performed receptor-based molecular docking of chemokine receptor 7 against natural and marine compounds. Semiquantitative polymerase chain reaction (PCR) and quantitative real-time PCR were performed for mRNA expression of chemokine receptor 7 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) used as internal control. The best-docked compounds have been selected for chemokine receptor 7 inhibitors by optimal energy value (Gscore), types of interactions, and conformations. CID6441009, 42607750, 72276, 6711419, 56835050, 65064, 23663412, 72277, 643668, 54679285 compound have a better binding energy ?11.35, ?10.51, ?10.16, ?9.98, ?9.95, ?9.86, ?9.83, ?9.57, ?9.47, and ?9.45 respectively against chemokine receptor 7. Protein?ligand interactions profile highlighted that amino acid Glu45, Lys50, Arg54, Lys57, Trp114, Met260, Glu205, Gln227, Gln276, and Asp309 involved in the hydrophobic, hydrogen bonding, and ?-? stacking interactions play a central role at the active site. Moreover, treatment with the Epigallocatechin gallate led to down-regulation of mRNA expression of chemokine receptor 7 in HepG2 and PC3 cells. This molecular docking study recapitulates the docking free energy, protein?ligands interactions profile, pharmacokinetic, and the pharmacodynamic parameter of lead molecules, which are extremely helpful to improve the activity of natural and marine compounds against chemokine receptor 7. ? 2016, Springer Science+Business Media New York.
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    Molecular Docking Study of Natural Compounds against Non Receptor Protein Tyrosine Kinases Src
    (Pharma Scholars Library, 2015) Bast, Felix; Singh, Pushpendra
    Non-receptor tyrosine kinases Src family plays an important role in signal transduction induced by diverse extracellular stimulus, including cytokine, and growth factors. Overactivity or overexpression of the non-receptor tyrosine kinase Src is involved in the growth, development and progression of various human cancers and their inhibitors are under intensive investigations as novel anti-cancer agents. Therefore, we studied receptor-based molecular docking of src against natural compounds. Each Selected compounds docked with the X-ray crystal structure of Src (PDB; 3EL7). The best-docked compounds have been elected for target by optimal energy value, types of interactions, and conformations. STOCK1N-75795, STOCK1N-80087, STOCK1N-72227, STOCK1N-79428, STOCK1N-72232, STOCK1N-72129, and STOCK1N-72552 compound have a better binding energy as well as binding conformation against src. Foremost, STOCK1N-80087, STOCK1N-72227, and STOCK1N-72232 are their excellent QPlogPo/w, CIQPlogS, QPlog HERG K+ channels, QPPCaco, QPlogBB, QPPMDCK, QPlogKP, QPlogKhsa and percentage of human oral absorption values which satisfy the Lipinski’s Rule of Five. This molecular docking study recapitulates docking free energy, protein ligands interaction profile, pharmacokinetic, and pharmacodynamic parameter of lead molecules, which are tremendously helpful to improve activity of natural compounds against src.
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    IMPACT OF PERSONALIZED MEDICINE IN CANCER
    (Nova Science Publishers, 2017) Singh, Pushpendra; Rani, Alka; Bast, Felix
    Personalized medicine aims to customize therapeutic care based on a person's unique genetic profile. Physicians have tailored care based on individual's health history and the environment. However, the decoding of the human genome in 2003 was an important step towards breakthroughs in personalized medicine, as a clinical care that takes benefits of molecular tools to facilitate highly specific health care based on individual's unique genomic and molecular characteristics. Pharmacogenetics refers to a single gene that influences drug metabolism. However, pharmacogenomics encompasses all genes in the genome that may determine the drug response. Pharmacogenomics enables the improved understanding of disease pathogenesis through genomics research, via identification of new biomarkers for cancer diagnosis. Pharmacogenetics and pharmacogenomics are around to revolutionize the aspect of medicine; yet, many challenges stand in the way. Hike in the cost of genotyping make genetic profiling less attractive and its clinical implementation is also lagging far behind. This book chapter presents an overview of the opportunities and challenges that influence the participation of personalized approach of giving the right drug at the right dose to the right patient. 
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    INFLUENCE OF INSULIN AND METFORMIN ON PROSTATE CANCER
    (Nova Science Publishers, 2017) Singh, Pushpendra; Bast, Felix; Kumar, Shashank; Saini, Khem Chand
    Dietary habit and hormonal factor play a significant role in prostate cancer deregulation in addition to genetic and environmental factor. Nonandrogenic growth factor like insulin and insulin growth factor are influences the prostate cancer initiation and progression. Insulin and Insulin-like growth factor regulate various metabolic pathways, cell growth, cellular proliferation and apoptosis. Various epidemiological results point out that insulin not only increased the risk of cardiovascular, macrovascular, and microvascular complications but also at significantly increase the risk of various cancers. The use of metformin, the usually approved drug for type 2 diabetes, was continually linked with the decreased risk of the incidence of a variety of cancers. More than 60 clinical trials of metformin being tested as a treatment for various types of cancer, including breast, colon, prostate, endometrial, and pancreatic cancer. The ability of metformin to lower circulating insulin may be predominantly imperative for the treatment of cancers. Moreover, metformin inhibiting mammalian target of rapamycin promoted cell growth signaling. In this chapter, the confirmation behind a role for metformin in cancer therapy and its prospective molecular mechanisms of action are discussed.