Synthesis,anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
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| Affiliation: | 1. Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad 500090, India;2. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore;3. School of Pharmacy, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Selangor, WA 46150, Malaysia;1. Institute of Chemical Engineering, Ural Federal University, 620002 Ekaterinburg, Russian Federation;2. Ural State Medical University, 620028 Ekaterinburg, Russian Federation;3. Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation;1. A. I. Herzen State Pedagogical University of Russia, 191186 St. Petersburg, Russian Federation;2. Department of Crystallography, St. Petersburg State University, 199034 St. Petersburg, Russian Federation;1. Key Lab of Inorganic Functional Material in Universities of Shandong, School of Material Science and Engineering, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China;2. Stephenson Institute for Renewable Energy, Department of Chemistry, University of Liverpool, Peach Street, Liverpool L69 7ZF, UK;1. Department of Physics and Measurements, Institute of Chemical Technology Prague, Technicka 5, Prague 6 CZ-166 28, Czech Republic;2. Department of Analysis of Functional Materials, Institute of Physics AS CR v.v.i, Na Slovance 1999/2, Prague 8 CZ-182 21, Czech Republic |
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| 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 μM). 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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| Keywords: | Heterobicyclic system Annulation reaction Thymidine phosphorylase inhibitors Angiogenesis Molecular docking |
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