Synthesis, molecular docking study and thymidine phosphorylase inhibitory activity of 3-formylcoumarin derivatives

• Published in: Bioorganic Chemistry
• Main Author: Taha M.; Adnan Ali Shah S.; Afifi M.; Imran S.; Sultan S.; Rahim F.; Hadiani Ismail N.; Mohammed Khan K.
• Format: Article
• Language: English
• Published: Academic Press Inc. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042907693&doi=10.1016%2fj.bioorg.2018.02.028&partnerID=40&md5=9b94f4076ef61fbd0fc443e4ff380a96

Thymidine phosphorylase (TP) over expression plays role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. The inhibitor of this enzyme plays an important role in preventing the serious threat due to over expression of TP. In this regard, a series of seventeenanalogs of 3-formylcoumarin (1–17) were synthesized, characterized by 1HNMR and EI-MS and screened for thymidine phosphorylaseinhibitory activity. All analogs showed a variable degree of thymidine phosphorylase inhibition with IC50 values ranging between 0.90 ± 0.01 and 53.50 ± 1.20 μM when compared with the standard inhibitor 7-Deazaxanthine having IC50 value 38.68 ± 1.12 μM. Among the series, fifteenanalogs such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16 and 17 showed excellent inhibition which is many folds better than the standard 7-Deazaxanthine whiletwo analogs 13 and 14 showed good inhibition. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl ring. Molecular docking study was carried out to understand the binding interaction of the most active analogs. © 2018 Elsevier Inc.