In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase

In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase

Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1–28) has been developed and evaluated against thymidine phosphorylase enzy...

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Published in:Bioorganic Chemistry
Main Author: Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
Format: Article
Language:English
Published: Academic Press Inc. 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979619091&doi=10.1016%2fj.bioorg.2016.07.010&partnerID=40&md5=40ed2677dc1df64b71178e6fc7babcd0
id 2-s2.0-84979619091
spelling 2-s2.0-84979619091
Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
2016
Bioorganic Chemistry
68

10.1016/j.bioorg.2016.07.010
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979619091&doi=10.1016%2fj.bioorg.2016.07.010&partnerID=40&md5=40ed2677dc1df64b71178e6fc7babcd0
Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1–28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20 ± 0.30 and 37.60 ± 1.15 μM when compared with the standard 7-Deazaxanthine (IC50 = 38.68 ± 4.42 μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX. © 2016 Elsevier Inc.
Academic Press Inc.
452068
English
Article
author Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
spellingShingle Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
author_facet Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
author_sort Taha M.; Ismail N.H.; Imran S.; Rahim F.; Wadood A.; Al Muqarrabun L.M.R.; Khan K.M.; Ghufran M.; Ali M.
title In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
title_short In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
title_full In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
title_fullStr In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
title_full_unstemmed In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
title_sort In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
publishDate 2016
container_title Bioorganic Chemistry
container_volume 68
container_issue
doi_str_mv 10.1016/j.bioorg.2016.07.010
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979619091&doi=10.1016%2fj.bioorg.2016.07.010&partnerID=40&md5=40ed2677dc1df64b71178e6fc7babcd0
description Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1–28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20 ± 0.30 and 37.60 ± 1.15 μM when compared with the standard 7-Deazaxanthine (IC50 = 38.68 ± 4.42 μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX. © 2016 Elsevier Inc.
publisher Academic Press Inc.
issn 452068
language English
format Article
accesstype
record_format scopus
collection Scopus
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