Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies

A series of benzothiazole based oxadiazole analogs 1-20 was synthesized by reacting intermediate sulfite adducts with 2-aminothiophenol and refluxing in DMF for 12 h to afford ester analog I which, on further refluxing in methanolic hydrazine hydrate solution, afforded compound II. Compound II was t...

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Published in:RSC Advances
Main Author: Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
Format: Article
Language:English
Published: Royal Society of Chemistry 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953923975&doi=10.1039%2fc5ra23072a&partnerID=40&md5=57f7d191e961c2f3fc5764f5bf504ec7
id 2-s2.0-84953923975
spelling 2-s2.0-84953923975
Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
2016
RSC Advances
6
4
10.1039/c5ra23072a
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953923975&doi=10.1039%2fc5ra23072a&partnerID=40&md5=57f7d191e961c2f3fc5764f5bf504ec7
A series of benzothiazole based oxadiazole analogs 1-20 was synthesized by reacting intermediate sulfite adducts with 2-aminothiophenol and refluxing in DMF for 12 h to afford ester analog I which, on further refluxing in methanolic hydrazine hydrate solution, afforded compound II. Compound II was then condensed with different aromatic carboxylic acids in POCl3 to synthesize novel benzothiazole based oxadiaxole derivatives 1-20 in good yields. All compounds were screened for β-glucuronidase inhibitory potential. Compounds 7, 14, 8 and 17 were found to be the most active analogs among the series with micromolar activities (IC50 = 2.16, 4.38, 7.20 and 8.56 μM, respectively). While compounds 5, 10, 18, 16, 1, 2, 15, 11, and 20 showed moderate activity with (IC50 values ranging between 14.12-75.14 μM), whereas compounds 3, 12, 13, and 19 were found to be inactive. Further studies showed that they do not possess any cytotoxic properties. Molecular docking studies were done to reveal the binding modes of the synthetic benzothiazole derivatives 1-20 targeting the active site of β-glucuronidase (PDB code: 1BHG). © The Royal Society of Chemistry 2016.
Royal Society of Chemistry
20462069
English
Article

author Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
spellingShingle Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
author_facet Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
author_sort Taha M.; Ismail N.H.; Imran S.; Selvaraj M.; Rahim F.
title Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
title_short Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
title_full Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
title_fullStr Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
title_full_unstemmed Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
title_sort Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies
publishDate 2016
container_title RSC Advances
container_volume 6
container_issue 4
doi_str_mv 10.1039/c5ra23072a
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84953923975&doi=10.1039%2fc5ra23072a&partnerID=40&md5=57f7d191e961c2f3fc5764f5bf504ec7
description A series of benzothiazole based oxadiazole analogs 1-20 was synthesized by reacting intermediate sulfite adducts with 2-aminothiophenol and refluxing in DMF for 12 h to afford ester analog I which, on further refluxing in methanolic hydrazine hydrate solution, afforded compound II. Compound II was then condensed with different aromatic carboxylic acids in POCl3 to synthesize novel benzothiazole based oxadiaxole derivatives 1-20 in good yields. All compounds were screened for β-glucuronidase inhibitory potential. Compounds 7, 14, 8 and 17 were found to be the most active analogs among the series with micromolar activities (IC50 = 2.16, 4.38, 7.20 and 8.56 μM, respectively). While compounds 5, 10, 18, 16, 1, 2, 15, 11, and 20 showed moderate activity with (IC50 values ranging between 14.12-75.14 μM), whereas compounds 3, 12, 13, and 19 were found to be inactive. Further studies showed that they do not possess any cytotoxic properties. Molecular docking studies were done to reveal the binding modes of the synthetic benzothiazole derivatives 1-20 targeting the active site of β-glucuronidase (PDB code: 1BHG). © The Royal Society of Chemistry 2016.
publisher Royal Society of Chemistry
issn 20462069
language English
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