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

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

doi:10.20944/preprints201901.0086.v1

A peer-reviewed article of this Preprint also exists.

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. Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study. Molecules 2019, 24, 1002. 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. Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study. Molecules 2019, 24, 1002.

Abstract

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR 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 analog 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, 21and 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.

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

Abstract

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