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  1. Article ; Online: Clerodane Furanoditerpenoids from

    Kabbashi, Ahmed Saeed / Sattar, Maazah Abdul / Aamer, Muhammad / Siddiqui, Nimra Naz / Kamran, Muhammad / Fayaz, Aneela / Jahan, Humera / Khan, Farooq-Ahmad / Wang, Yan

    Molecules (Basel, Switzerland)

    2023  Volume 29, Issue 1

    Abstract: Tinospora ... ...

    Abstract Tinospora bakis
    MeSH term(s) Animals ; Tinospora ; Menispermaceae ; Diterpenes, Clerodane/pharmacology ; Coleoptera ; Glucose
    Chemical Substances Diterpenes, Clerodane ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-12-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules29010154
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  2. Article: Indole-linked 1,2,3-triazole derivatives efficiently modulate COX-2 protein and PGE2 levels in human THP-1 monocytes by suppressing AGE-ROS-NF-kβ nexus

    Jahan, Humera / Siddiqui, Nimra Naz / Iqbal, Shazia / Basha, Fatima Z. / Khan, Maria Aqeel / Aslam, Tooba / Choudhary, M. Iqbal

    Life sciences. 2022 Feb. 15, v. 291

    2022  

    Abstract: AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in AGEs- ... ...

    Abstract AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in AGEs-induced inflammation. Initially, the analogs 2-13 were synthesized by cycloaddition reaction between prop-2-yn-1-yl-2-(1H-indol-3-yl) acetate (1) and azidoacetophenone (1a). In vitro glycation, and metabolic assays were employed to investigate antiglycation and cytotoxicity activities of new indole-triazoles. DCFH-DA, immunostaining, Western blotting, and ELISA techniques were used to study the reactive oxygen species (ROS), and pro-inflammatory mediators levels. Among all the synthesized indole-triazoles, compounds 1-3, and 9-13, and their precursor molecule 1 were found to be active against AGEs production in in vitro glucose- and methylglyoxal (MGO)-BSA models. Compounds 1-2, and 11-13 were also found to be nontoxic against HEPG2, and THP-1 cells. Our results show that pretreatment of THP-1 monocytes with selected lead compounds 1-2, and 11-13, particularly compounds 12, and 13, reduced glucose- and MGO-derived AGEs-mediated ROS production (P < 0.001), as compared to standards, PDTC, rutin, and quercetin. They also significantly (P < 0.001) suppressed NF-ĸB translocation in THP-1 monocytes. Moreover, compounds 12, and 13 attenuated the AGEs-induced COX-2 protein levels (P < 0.001), and PGE₂ production (P < 0.001) in THP-1 monocytes. Our data revealed that the indole-triazoles 12, and 13 can significantly attenuate the AGEs-induced proinflammatory COX-2 levels, and associated PGE₂ production by suppressing AGE-ROS-NF-Kβ nexus in THP-1 monocytes. These compounds can thus serve as leads for further evaluation as treatment to delay early onset of diabetic complications.
    Keywords cycloaddition reactions ; cytotoxicity ; glycation ; humans ; inflammation ; monocytes ; quercetin ; reactive oxygen species ; rutin
    Language English
    Dates of publication 2022-0215
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2021.120282
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    In stock of ZB MED Bonn / Germany

    Z 73/732: Show issues

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  3. Article ; Online: Suppression of COX-2/PGE

    Jahan, Humera / Siddiqui, Nimra Naz / Iqbal, Shazia / Basha, Fatima Z / Shaikh, Sadia / Pizzi, Marina / Choudhary, M Iqbal

    Cellular signalling

    2022  Volume 97, Page(s) 110372

    Abstract: Chronic hyperglycemia favours the formation of advanced glycation end products (AGEs) which are responsible of many diabetic vascular complications. Keeping in view the medicinal properties of the1,2,3-triazole-conjugated analogs, the present study was ... ...

    Abstract Chronic hyperglycemia favours the formation of advanced glycation end products (AGEs) which are responsible of many diabetic vascular complications. Keeping in view the medicinal properties of the1,2,3-triazole-conjugated analogs, the present study was designed to evaluate the possible effect of carbazole-linked 1,2,3-triazoles 2-16 against glucose- and methylglyoxal-AGEs-induced inflammation in human THP-1 monocytes. In vitro antiglycation, and metabolic assays were used to determine antiglycation, and cytotoxicity activities. DCFH-DA, immunostaining, immunoblotting, and ELISA techniques were employed to study the ROS and levels of proinflammatory mediators in THP-1 monocytes. Among all the synthesized carbazole-linked 1,2,3 triazoles, compounds 2, 7, 8, and 11-16 showed antiglycation activity in glucose- and MGO-modified bovine serum albumin models, whereas parent compound 1 only exhibited activity in glucose-BSA model. The metabolic assay demonstrated the non-toxic profile of compounds 1-2, 11-13, and 15 up to 100 μM concentration in both HepG2 and THP-1 cell lines. We found that compounds 11-13, and 15 attenuated AGEs-induced ROS formation (P < 0.001), and halted NF-ĸB translocation (P < 0.001), likewise standard drugs, PDTC, rutin, and quercetin, in THP-1 monocytes. Among the derivatives, compounds 12, and 13 also suppressed the AGEs-induced elevation of COX-2 (P < 0.001) and PGE
    MeSH term(s) Carbazoles/metabolism ; Carbazoles/pharmacology ; Cyclooxygenase 2/metabolism ; Diabetic Angiopathies/metabolism ; Dinoprostone/metabolism ; Glucose/metabolism ; Glycation End Products, Advanced ; Humans ; Monocytes/metabolism ; NF-kappa B/metabolism ; Pyruvaldehyde/pharmacology ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Triazoles/pharmacology
    Chemical Substances Carbazoles ; Glycation End Products, Advanced ; NF-kappa B ; Reactive Oxygen Species ; Triazoles ; Pyruvaldehyde (722KLD7415) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Glucose (IY9XDZ35W2) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2022-05-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1002702-6
    ISSN 1873-3913 ; 0898-6568
    ISSN (online) 1873-3913
    ISSN 0898-6568
    DOI 10.1016/j.cellsig.2022.110372
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2579: 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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  4. Article ; Online: Indole-linked 1,2,3-triazole derivatives efficiently modulate COX-2 protein and PGE

    Jahan, Humera / Siddiqui, Nimra Naz / Iqbal, Shazia / Basha, Fatima Z / Khan, Maria Aqeel / Aslam, Tooba / Choudhary, M Iqbal

    Life sciences

    2022  Volume 291, Page(s) 120282

    Abstract: Aims: AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in ...

    Abstract Aims: AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in AGEs-induced inflammation.
    Material and methods: Initially, the analogs 2-13 were synthesized by cycloaddition reaction between prop-2-yn-1-yl-2-(1H-indol-3-yl) acetate (1) and azidoacetophenone (1a). In vitro glycation, and metabolic assays were employed to investigate antiglycation and cytotoxicity activities of new indole-triazoles. DCFH-DA, immunostaining, Western blotting, and ELISA techniques were used to study the reactive oxygen species (ROS), and pro-inflammatory mediators levels.
    Key findings: Among all the synthesized indole-triazoles, compounds 1-3, and 9-13, and their precursor molecule 1 were found to be active against AGEs production in in vitro glucose- and methylglyoxal (MGO)-BSA models. Compounds 1-2, and 11-13 were also found to be nontoxic against HEPG2, and THP-1 cells. Our results show that pretreatment of THP-1 monocytes with selected lead compounds 1-2, and 11-13, particularly compounds 12, and 13, reduced glucose- and MGO-derived AGEs-mediated ROS production (P < 0.001), as compared to standards, PDTC, rutin, and quercetin. They also significantly (P < 0.001) suppressed NF-ĸB translocation in THP-1 monocytes. Moreover, compounds 12, and 13 attenuated the AGEs-induced COX-2 protein levels (P < 0.001), and PGE
    Significance: Our data revealed that the indole-triazoles 12, and 13 can significantly attenuate the AGEs-induced proinflammatory COX-2 levels, and associated PGE
    MeSH term(s) Cyclooxygenase 2/metabolism ; Cytokines/metabolism ; Dinoprostone/metabolism ; Glycation End Products, Advanced/drug effects ; Glycation End Products, Advanced/metabolism ; Humans ; Indoles/chemistry ; Indoles/pharmacology ; Inflammation/metabolism ; Inflammation Mediators/metabolism ; Monocytes/metabolism ; NF-kappa B/metabolism ; Reactive Oxygen Species/metabolism ; THP-1 Cells ; Triazoles/chemistry ; Triazoles/pharmacology
    Chemical Substances Cytokines ; Glycation End Products, Advanced ; Indoles ; Inflammation Mediators ; NF-kappa B ; Reactive Oxygen Species ; Triazoles ; Cyclooxygenase 2 (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2022-01-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2021.120282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.368: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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