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

• Published in: Molecules
• Main Author: Almandil N.B.; Taha M.; Farooq R.K.; Alhibshi A.; Ibrahim M.; Anouar E.H.; Gollapalli M.; Rahim F.; Nawaz M.; Shah S.A.A.; Ahmed Q.U.; Zakaria Z.A.
• Format: Article
• Language: English
• Published: MDPI AG 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062955700&doi=10.3390%2fmolecules24061002&partnerID=40&md5=ef4631fe73f2a47cb1b36fec4203f36b
• ISSN: 14203049
• DOI: 10.3390/molecules24061002

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. © 2019 by the authors.