Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones

Hriday Bera, Min Huey Lee, Lingyi Sun, Anton V Dolzhenko, Wai-Keung Chui

    Research output: Contribution to journalArticleResearchpeer-review

    13 Citations (Scopus)

    Abstract

    In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.
    Original languageEnglish
    Pages (from-to)34 - 40
    Number of pages7
    JournalBioorganic Chemistry
    Volume50
    DOIs
    Publication statusPublished - 2013

    Cite this

    Bera, Hriday ; Lee, Min Huey ; Sun, Lingyi ; Dolzhenko, Anton V ; Chui, Wai-Keung. / Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones. In: Bioorganic Chemistry. 2013 ; Vol. 50. pp. 34 - 40.
    @article{6b48963d1f4c4dcca2a4b3f771982bce,
    title = "Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones",
    abstract = "In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.",
    author = "Hriday Bera and Lee, {Min Huey} and Lingyi Sun and Dolzhenko, {Anton V} and Wai-Keung Chui",
    year = "2013",
    doi = "10.1016/j.bioorg.2013.07.004",
    language = "English",
    volume = "50",
    pages = "34 -- 40",
    journal = "Bioorganic Chemistry",
    issn = "0045-2068",
    publisher = "Elsevier",

    }

    Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones. / Bera, Hriday; Lee, Min Huey; Sun, Lingyi; Dolzhenko, Anton V; Chui, Wai-Keung.

    In: Bioorganic Chemistry, Vol. 50, 2013, p. 34 - 40.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones

    AU - Bera, Hriday

    AU - Lee, Min Huey

    AU - Sun, Lingyi

    AU - Dolzhenko, Anton V

    AU - Chui, Wai-Keung

    PY - 2013

    Y1 - 2013

    N2 - In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.

    AB - In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.

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