Browsing by Author "Tripathi, Nancy"

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    LCMS-DNP based dereplication of Araucaria cunninghamii Mudie gum-resin: identification of new cytotoxic labdane diterpene
    (Taylor and Francis Ltd., 2022) Sahu, Bharat; Bhardwaj, Nivedita; Chatterjee, Essha; Dey, Biswajit; Tripathi, Nancy; Goel, Bharat; Kushwaha, Manoj; Kumar, Brijesh; Singh, Bikarma; Guru, Santosh Kumar; Jain, Shreyans K.
    As a part of natural defense, plants initiate the secretion of gum containing numerous pharmacologically active essential metabolites. A fraction of such gum-resin from Araucaria cunninghamii Mudie, when screened against human cancer cell lines, was found to be active. Further, it was subjected to an LCMS-DNP (Dictionary of Natural Products) based dereplication study followed by a detailed phytochemical investigation to obtain pure metabolites. Also, the gum resin of A. cunninghamii was found to be a rich source of abietanes and labdanes. The LCMS-DNP-based dereplication study identified many known metabolites, which were isolated for the first time from this plant as well as a new labdane diterpenoid (9). The compounds were characterized via spectroscopic techniques, which were subsequently compared with the already existing literature data. The metabolites were screened against seven human cancer cell lines. The anticancer activity was further supported by molecular docking studies. � 2022 Informa UK Limited, trading as Taylor & Francis Group.
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    Low expression of TMPRSS2�a SARS-CoV-2 internalization protease�associates with basal subtype of head and neck squamous cell carcinoma
    (Neoplasia Press, Inc., 2022) Tiwari, Jayesh; Tripathi, Nancy; Srivastava, Ravi Shanker; Kumar, Sujeet; Singh, Sanjay; Jain, Shreyans; Khattri, Arun
    SARS-CoV-2 is a single-stranded RNA virus that has caused the ongoing COVID-19 pandemic. ACE2 and other genes utilized by SARS-CoV-2 to enter human cells have been shown to express in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. However, their expression pattern in different subtypes has not been investigated. Hence, in the current study, we have analyzed the expression of ACE2, TMPRSS2 and FURIN in 649 HNSCC patients from two independent cohorts. Our analysis showed significantly lower expression of TMPRSS2 while significantly increased expression of ACE2 and FURIN in HPV-negative HNSCC. Comparison of expression of these genes in the three subtypes of HNSCC patients (basal, classical and inflamed/mesenchymal) showed no significant difference in the expression of ACE2 among the three subtypes; however, the basal subtype showed significantly reduced expression of TMPRSS2 but significantly increased expression of FURIN. Comparison of expression of these genes between the HPV-negative patients of basal subtype vs all others confirmed significantly lower expression of TMPRSS2 in HPV-negative patients of basal subtype as compared to all others. Our study shows that the different subtypes of HNSCC patients have different expression patterns of genes utilized by the SARS-CoV-2 to enter human cells, and hence, their susceptibility to SARS-CoV-2 may also be different. As the expression of TMPRSS2 is significantly lower in the HNSCC patients of the basal subtype, we predict that these patients would be less susceptible to SARS-CoV-2 infection than the patients of other subtypes. However, these findings need to be further validated. � 2022
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    Synthesis, in vitro Cytotoxicity Evaluation, and Docking Studies of Gloriosine Derivatives as Potential Anticancer Agents
    (John Wiley and Sons Inc, 2023) Goel, Bharat; Naik, Aliva; Tripathi, Nancy; Khan, Anjesh; Bansal, Sunil; Bansal, Shivani; Kumar Guru, Santosh; Jain, Shreyans K.
    In the present work, series of C10-amine and amide derivatives of gloriosine were synthesized and evaluated for in vitro cytotoxic activity against a panel of six human cancer cell lines (MDA-MB-231, U87, FaDu, SiHa, A549, and MCF-7) of multiple tissue origin. The synthesized compounds were characterized by 1H and 13C NMR and MS experiments. In vitro cytotoxicity study showed that most of the C10-amine derivatives demonstrated superior activity in two of the tested cell lines, namely U87 and FaDu cell lines, while C10-amide derivatives showed poor activity in all the cell lines. The C10-amine derivatives were subjected to molecular docking studies to explore their possible binding interactions with colchicine binding site of tubulin protein, and in-silico ADME profiling to study the drug-likeness. The C10-amine derivatives may be less toxic than gloriosine towards normal cells and may provide the lead for anticancer drug development. � 2023 Wiley-VCH GmbH.
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    Virtual screening and molecular simulation study of natural products database for lead identification of novel coronavirus main protease inhibitors
    (Taylor and Francis Ltd., 2022) Tripathi, Nancy; Goel, Bharat; Bhardwaj, Nivedita; Sahu, Bharat; Kumar, Hemant; Jain, Shreyans K.
    3CL like protease (3CLpro or Mpro) is one of the main proteases of 2019-nCoV. The 3CLpro is a nonstructural protein of SARS-CoV and has an essential role in viral replication and transcription, thus, could be a potential target for anti-SARS drug development. The present study employed ligand- and structure-based approaches to identify the potent inhibitors of 2019-nCoV protease. The e-pharmacophore developed from 3CLpro-1 yielded virtual hits, that were subjected through drug likeliness and PAINS filters to remove interfering compounds. Further comprehensive docking studies, free energy calculations and ADMET studies resulted in two virtual leads- MolPort-000-410-348 and MolPort-002-530-156. The compounds MolPort-000-410-348 and MolPort-002-530-156 displayed good docking score of ?12.09 and ?13.38 Kcal/mol and free binding energy of ?63.34 � 2.03 and ?61.52 � 2.24 Kcal/mol, respectively. The compounds also exhibited satisfactory predicted ADMET profile and were subjected to molecular dynamic (MD) studies. The MD simulation produced stable complexes of these ligands with 3CLpro protein and ligand RMSD in acceptable limits. Communicated by Ramaswamy H. Sarma. � 2020 Informa UK Limited, trading as Taylor & Francis Group.