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:10.3390/molecules24061002

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

Chemistry

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Article number	1002
Journal	Molecules
Volume	24
Issue number	6
DOIs	https://doi.org/10.3390/molecules24061002
State	Published - 2019

Keywords

Molecular docking
Quinoxaline analogs
Synthesis
Thymidine phosphorylase inhibition

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10.3390/molecules24061002

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title = "Synthesis of thymidine phosphorylase inhibitor based on quinoxaline derivatives and their molecular docking study",

abstract = "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.",

keywords = "Molecular docking, Quinoxaline analogs, Synthesis, Thymidine phosphorylase inhibition",

author = "Almandil, \{Noor Barak\} and Muhammad Taha and Farooq, \{Rai Khalid\} and Amani Alhibshi and Mohamed Ibrahim and Anouar, \{El Hassane\} and Mohammed Gollapalli and Fazal Rahim and Muhammad Nawaz and Shah, \{Syed Adnan Ali\} and Ahmed, \{Qamar Uddin\} and Zakaria, \{Zainul Amiruddin\}",

note = "Publisher Copyright: {\textcopyright} 2019 by the authors.",

year = "2019",

doi = "10.3390/molecules24061002",

language = "English",

volume = "24",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - Synthesis of thymidine phosphorylase inhibitor based on quinoxaline derivatives and their molecular docking study

AU - Almandil, Noor Barak

AU - Taha, Muhammad

AU - Farooq, Rai Khalid

AU - Alhibshi, Amani

AU - Ibrahim, Mohamed

AU - Anouar, El Hassane

AU - Gollapalli, Mohammed

AU - Rahim, Fazal

AU - Nawaz, Muhammad

AU - Shah, Syed Adnan Ali

AU - Ahmed, Qamar Uddin

AU - Zakaria, Zainul Amiruddin

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Molecular docking

KW - Quinoxaline analogs

KW - Synthesis

KW - Thymidine phosphorylase inhibition

UR - http://www.scopus.com/inward/record.url?scp=85062955700&partnerID=8YFLogxK

U2 - 10.3390/molecules24061002

DO - 10.3390/molecules24061002

M3 - Article

C2 - 30871147

AN - SCOPUS:85062955700

SN - 1420-3049

VL - 24

JO - Molecules

JF - Molecules

IS - 6

M1 - 1002

ER -

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

Abstract

Keywords

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