Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

• Main Authors: Noor Barak Almandil, Muhammad Taha, Rai Khalid Farooq, Amani Alhibshi, Mohamed Ibrahim, El Hassane Anouar, Mohammed Gollapalli, Fazal Rahim, Muhammad Nawaz, Syed Adnan Ali Shah, Qamar Uddin Ahmed, Zainul Amiruddin Zakaria
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: Molecules
• Subjects: quinoxaline analogs; synthesis; thymidine phosphorylase inhibition; molecular docking
• Online Access: http://www.mdpi.com/1420-3049/24/6/1002

We have synthesized quinoxaline analogs (1–25), characterized by 1H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.