Synthesis of thymidine phosphorylase inhibitor based on quinoxaline derivatives and their molecular docking study

• Main Authors: Almandil, Noor Barak, Taha, Muhammad, Farooq, Rai Khalid, Alhibshi, Amani, Ibrahim, Mohamed, Anouar, El Hassane, Gollapalli, Mohammed, Rahim, Fazal, Nawaz, Muhammad, Shah, Syed Adnan Ali, Ahmed, Qamar Uddin, Zakaria, Zainul Amiruddin
• Format: Article
• Language: English
• Published: MDPI 2019
• Online Access: http://psasir.upm.edu.my/id/eprint/38421/1/38421.pdf; http://psasir.upm.edu.my/id/eprint/38421/; https://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.