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  1. Article ; Online: Physicochemical characterization of paclitaxel prodrugs with cytochrome 3A4 to correlate solubility and bioavailability implementing molecular docking and simulation studies.

    Munjal, Nupur S / Shukla, Rohit / Singh, Tiratha Raj

    Journal of biomolecular structure & dynamics

    2021  Volume 40, Issue 13, Page(s) 5983–5995

    Abstract: Prodrugs are biologically inactive drug molecules that may be developed through rational drug design with an objective to improve a drug's pharmaceutical and pharmacokinetic properties. Paclitaxel, a highly potent anticancer drug, is directed against ... ...

    Abstract Prodrugs are biologically inactive drug molecules that may be developed through rational drug design with an objective to improve a drug's pharmaceutical and pharmacokinetic properties. Paclitaxel, a highly potent anticancer drug, is directed against many cancers like breast cancer, ovarian cancer, lung cancer, head and neck tumors, non-small cell lung cancer, and Kaposi's sarcoma, etc. Along with its excellent antitumor activity the drug had a major limitation of low water solubility. To overcome this limitation of this nanomolar active drug many prodrugs were formed in the past. Though increase in the solubility of the drug was obtained but that may or may not account for its increase in bioavailability. CYP3A4 liver enzymes are responsible for the metabolism of fifty percent of the drugs and are major metabolizing enzyme for paclitaxel. Phosphate prodrugs are well known to account the insolubility of many drugs and thus increasing their bioavailability also. In this study, we calculated the ADMET properties of a dataset of twenty phosphate prodrugs of paclitaxel. On the basis of reflection of three favourable properties, ten prodrugs were chosen for further docking studies against CYP3A4. Finally, three prodrugs showing unfavourable binding affinities were selected for Molecular Dynamics Simulations and from this
    MeSH term(s) Biological Availability ; Cytochrome P-450 CYP3A/chemistry ; Humans ; Molecular Docking Simulation ; Paclitaxel/chemistry ; Paclitaxel/pharmacokinetics ; Phosphates ; Prodrugs/chemistry ; Prodrugs/pharmacokinetics ; Solubility
    Chemical Substances Phosphates ; Prodrugs ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2021.1875881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Identification of novel small molecules against GSK3β for Alzheimer's disease using chemoinformatics approach.

    Shukla, Rohit / Munjal, Nupur S / Singh, Tiratha Raj

    Journal of molecular graphics & modelling

    2019  Volume 91, Page(s) 91–104

    Abstract: Alzheimer's disease is a rapidly increasing neurodegenerative disease. It is a multifactorial disease and also a global threat. Several enzymes are implicated in the disease in which Glycogen Synthase Kinase 3 beta is a key enzyme to increase the disease ...

    Abstract Alzheimer's disease is a rapidly increasing neurodegenerative disease. It is a multifactorial disease and also a global threat. Several enzymes are implicated in the disease in which Glycogen Synthase Kinase 3 beta is a key enzyme to increase the disease progression by the hyperphosphorylation of the tau protein. We have used an integrative chemoinformatics and pharmacokinetics approach for the identification of novel small molecules. We have retrieved a subset from the ZINC database (n = 5,36,709) and screened against GSK3β in four steps. From here top 298 potent compounds were selected and employed for their pharmacokinetics analysis. We had seen that 29 compounds showed the key characteristics to be a novel drug candidate therefore, all these compounds were employed for redocking studies using Autodock Vina and Autodock. This analysis revealed that four compounds were showing good binding affinity. All these four compounds were employed for MDS analysis of 100 ns From here using a bunch of MD analyses we have found that out of four compounds GSK3β-ZINC21011059 and GSK3β-ZINC21011066 act as a stable protein-ligand complex. Therefore we proposed ZINC21011059 and ZINC21011066 can serve as a novel compounds against GSK3β and predicted scaffold can be used for further optimization towards the improvement of isoform selectivity, and warranting further investigations towards their in vitro and in vivo validation of the bioactivity.
    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/enzymology ; Binding Sites ; Cheminformatics ; Drug Evaluation, Preclinical ; Enzyme Stability ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta/chemistry ; Humans ; Hydrogen Bonding ; Ligands ; Molecular Docking Simulation ; Principal Component Analysis ; Protein Conformation ; Small Molecule Libraries/analysis ; Small Molecule Libraries/pharmacokinetics ; Small Molecule Libraries/therapeutic use ; Solvents ; Thermodynamics
    Chemical Substances Ligands ; Small Molecule Libraries ; Solvents ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1)
    Language English
    Publishing date 2019-06-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1396450-1
    ISSN 1873-4243 ; 1093-3263
    ISSN (online) 1873-4243
    ISSN 1093-3263
    DOI 10.1016/j.jmgm.2019.06.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3491: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods

    Munjal, Nupur S. / Sapra, Dikscha / Parthasarathi, K. T. Shreya / Goyal, Abhishek / Pandey, Akhilesh / Banerjee, Manidipa / Sharma, Jyoti

    Pathogens. 2022 Feb. 17, v. 11, no. 2

    2022  

    Abstract: ... proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing a higher accuracy for host-SARS-CoV-2 protein–protein interactions (PPIs). In this study, PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were trained on the PPI-MetaGO algorithm. PPI networks (PPINs) and a signaling pathway map of HICs with SARS-CoV-2 proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs interacting with the potential HICs were identified. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient score (MCC) and 84.09% F1 score. Several host pathways were found to be altered, including calcium signaling and taste transduction pathway. Potential HICs could serve as an initial set to the experimentalists for further validation. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs that may provide a better therapeutic management strategy for infection caused by SARS-CoV-2.
    Keywords COVID-19 infection ; Food and Drug Administration ; Severe acute respiratory syndrome coronavirus 2 ; algorithms ; calcium ; drugs ; economic crises ; humans ; pathogenesis ; pathogenicity ; taste ; therapeutics
    Language English
    Dates of publication 2022-0217
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11020259
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods.

    Munjal, Nupur S / Sapra, Dikscha / Parthasarathi, K T Shreya / Goyal, Abhishek / Pandey, Akhilesh / Banerjee, Manidipa / Sharma, Jyoti

    Pathogens (Basel, Switzerland)

    2022  Volume 11, Issue 2

    Abstract: ... proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing a higher accuracy for host-SARS-CoV-2 protein-protein interactions (PPIs). In this study, PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were trained on the PPI-MetaGO algorithm. PPI networks (PPINs) and a signaling pathway map of HICs with SARS-CoV-2 proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs interacting with the potential HICs were identified. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient score (MCC) and 84.09% F1 score. Several host pathways were found to be altered, including calcium signaling and taste transduction pathway. Potential HICs could serve as an initial set to the experimentalists for further validation. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs that may provide a better therapeutic management strategy for infection caused by SARS-CoV-2.
    Language English
    Publishing date 2022-02-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11020259
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies.

    Mishra, Deepak / Maurya, Radha Raman / Kumar, Kamlesh / Munjal, Nupur S / Bahadur, Vijay / Sharma, Sandeep / Singh, Prashant / Bahadur, Indra

    Journal of molecular liquids

    2021  Volume 335, Page(s) 116185

    Abstract: Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world's economy and global health sector. Earlier the structure of main protease ( ... ...

    Abstract Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world's economy and global health sector. Earlier the structure of main protease (M
    Language English
    Publishing date 2021-04-16
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1491496-7
    ISSN 1873-3166 ; 0167-7322
    ISSN (online) 1873-3166
    ISSN 0167-7322
    DOI 10.1016/j.molliq.2021.116185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Development of QSPR Strategy for the Solubility Prediction.

    Munjal, Nupur S / Sharma, Manu / Singh, Tiratha Raj

    Current computer-aided drug design

    2018  Volume 14, Issue 4, Page(s) 302–309

    Abstract: Introduction: QSPR modelling is one of the major computational tools used to correlate molecular characteristics with physiochemical properties of molecules. In present work, QSPR models are formed using AIC and VIF multicollinearity indicators for ... ...

    Abstract Introduction: QSPR modelling is one of the major computational tools used to correlate molecular characteristics with physiochemical properties of molecules. In present work, QSPR models are formed using AIC and VIF multicollinearity indicators for descriptors selection taking solubility data of Paclitaxel prodrugs. Geometry optimization of these Paclitaxel prodrugs was performed at the PM6 and AM1levels using Gaussian software.
    Methods: Four descriptor groups such as 2D Autocorrelation, CATS_3D, WHIM, GETAWAY provided initial QSPR models with moderate accuracy for both the optimized geometry datasets. The descriptors from two descriptor-groups which were showing reasonable correlation (Q2) were combined to form improved models. The selection of descriptors was performed in multiple steps to determine optimal models which contain five and four descriptors for PM6 and AM1 optimized geometry datasets respectively. The R2 & Q2 values are 0.86 & 0.83 and 0.87 & 0.86 for PM6 and AM1 geometries respectively.
    Results: The models formed shows comparable results with the earlier reported results. The proposed protocol is also implemented on Huuskonen small dataset and the final QSPR model contains only two descriptors. On this smaller dataset, the QSPR model gives the R2 and Q2 values 0.87 and 0.85, respectively which is comparable to the results of Paclitaxel prodrugs.
    Conclusion: Our approach can be applicable to different datasets and it can assist the synthesis of molecule with better solubility. These QSPR models can be implemented for predicting the aqueous solubility of unknown Paclitaxel prodrugs.
    MeSH term(s) Algorithms ; Antineoplastic Agents, Phytogenic/chemistry ; Computer Simulation ; Models, Chemical ; Paclitaxel/chemistry ; Prodrugs/chemistry ; Quantitative Structure-Activity Relationship ; Software ; Solubility ; Water/chemistry
    Chemical Substances Antineoplastic Agents, Phytogenic ; Prodrugs ; Water (059QF0KO0R) ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2018-08-29
    Publishing country United Arab Emirates
    Document type Journal Article
    ISSN 1875-6697
    ISSN (online) 1875-6697
    DOI 10.2174/1573409914666180713114954
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods

    Nupur S. Munjal / Dikscha Sapra / K. T. Shreya Parthasarathi / Abhishek Goyal / Akhilesh Pandey / Manidipa Banerjee / Jyoti Sharma

    Pathogens, Vol 11, Iss 259, p

    2022  Volume 259

    Abstract: ... proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing a higher accuracy for host-SARS-CoV-2 protein–protein interactions (PPIs). In this study, PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were trained on the PPI-MetaGO algorithm. PPI networks (PPINs) and a signaling pathway map of HICs with SARS-CoV-2 proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs interacting with the potential HICs were identified. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient score (MCC) and 84.09% F1 score. Several host pathways were found to be altered, including calcium signaling and taste transduction pathway. Potential HICs could serve as an initial set to the experimentalists for further validation. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs that may provide a better therapeutic management strategy for infection caused by SARS-CoV-2.
    Keywords virus and host ; protein interaction networks ; cellular pathways ; antiviral compounds ; Medicine ; R
    Subject code 572
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: A pathway map of signaling events triggered upon SARS-CoV infection.

    Parthasarathi, K T Shreya / Munjal, Nupur S / Dey, Gourav / Kumar, Abhishek / Pandey, Akhilesh / Balakrishnan, Lavanya / Sharma, Jyoti

    Journal of cell communication and signaling

    2021  Volume 15, Issue 4, Page(s) 595–600

    Abstract: Severe acute respiratory syndrome coronaviruses (SARS-CoVs) caused worldwide epidemics over the past few decades. Extensive studies on various strains of coronaviruses provided a basic understanding of the pathogenesis of the disease. Presently, severe ... ...

    Abstract Severe acute respiratory syndrome coronaviruses (SARS-CoVs) caused worldwide epidemics over the past few decades. Extensive studies on various strains of coronaviruses provided a basic understanding of the pathogenesis of the disease. Presently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading a global pandemic with unprecedented challenges. This is the third coronavirus outbreak of this century. A signaling pathway map of signaling events induced by SARS-CoV infection is not yet available. In this study, we present a literature-annotated signaling pathway map of reactions induced by SARS-CoV infected cells. Multiple signaling modules were found to be orchestrated including PI3K-AKT, Ras-MAPK, JAK-STAT, Type 1 IFN and NFκB. The signaling pathway map of SARS-CoV consists of 110 molecules and 101 reactions mediated by SARS-CoV proteins. The pathway reaction data are available in various community standard data exchange formats including Systems Biology Graphical Notation (SBGN). The pathway map is publicly available through the GitHub repository and data in various formats can be freely downloadable.
    Language English
    Publishing date 2021-09-06
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2299380-0
    ISSN 1873-961X ; 1873-9601
    ISSN (online) 1873-961X
    ISSN 1873-9601
    DOI 10.1007/s12079-021-00642-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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