Synthesis of new isoquinoline-base-oxadiazole derivatives as potent inhibitors of thymidine phosphorylase and molecular docking study

• Published in: Scientific reports 2019-11, Vol.9 (1), p.16015-11, Article 16015
• Main Authors: Zaman, Khalid, Rahim, Fazal, Taha, Muhammad, Wadood, Abdul, Shah, Syed Adnan Ali, Ahmed, Qamar Uddin, Zakaria, Zainul Amiruddin
• Format: Article
• Language: English
• Subjects: 140/131; 631/45/607; 639/638/309/606; Angiogenesis; Binding Sites; Cancer therapies; Chemistry; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - metabolism; Enzymes; Escherichia coli - enzymology; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; FDA approval; Humanities and Social Sciences; Humans; Inflammatory diseases; Inhibitory Concentration 50; Isoquinolines - chemistry; Kinases; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; multidisciplinary; NMR; Nuclear magnetic resonance; Oxadiazoles - chemistry; Oxadiazoles - metabolism; Pharmacy; Phosphorylase; Protein Structure, Tertiary; Psoriasis; Rheumatoid arthritis; Science; Science (multidisciplinary); Skin diseases; Structure-Activity Relationship; Thymidine; Thymidine phosphorylase; Thymidine Phosphorylase - chemistry; Thymidine Phosphorylase - metabolism; Vascular endothelial growth factor; Xanthines - chemistry; Xanthines - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52100-0

Here in this study regarding the over expression of TP, which causes some physical, mental and socio problems like psoriasis, chronic inflammatory disease, tumor angiogenesis and rheumatoid arthritis etc . By this consideration, the inhibition of this enzyme is vital to secure life from serious threats. In connection with this, we have synthesized twenty derivatives of isoquinoline bearing oxadiazole (1–20), characterized through different spectroscopic techniques such as HREI-MS, 1 H- NMR and 13 C-NMR and evaluated for thymidine phosphorylase inhibition. All analogues showed outstanding inhibitory potential ranging in between 1.10 ± 0.05 to 54.60 ± 1.50  µ M. 7-Deazaxanthine (IC 50  = 38.68 ± 1.12  µ M) was used as a positive control. Through limited structure activity relationships study, it has been observed that the difference in inhibitory activities of screened analogs are mainly affected by different substitutions on phenyl ring. The effective binding interactions of the most active analogs were confirmed through docking study.