Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study

Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study

A new series of oxadiazole with thiadiazole moiety (6–27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the rang...

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Published in:Bioorganic and Medicinal Chemistry
Main Author: Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
Format: Article
Language:English
Published: Elsevier Ltd 2019
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066996057&doi=10.1016%2fj.bmc.2019.05.049&partnerID=40&md5=ecd950b1a53d346832bbb97fc0a2db8b
id 2-s2.0-85066996057
spelling 2-s2.0-85066996057
Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
2019
Bioorganic and Medicinal Chemistry
27
14
10.1016/j.bmc.2019.05.049
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066996057&doi=10.1016%2fj.bmc.2019.05.049&partnerID=40&md5=ecd950b1a53d346832bbb97fc0a2db8b
A new series of oxadiazole with thiadiazole moiety (6–27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition. © 2019 Elsevier Ltd
Elsevier Ltd
09680896
English
Article
author Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
spellingShingle Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
author_facet Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
author_sort Taha M.; Imran S.; Alomari M.; Rahim F.; Wadood A.; Mosaddik A.; Uddin N.; Gollapalli M.; Alqahtani M.A.; Bamarouf Y.A.
title Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
title_short Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
title_full Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
title_fullStr Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
title_full_unstemmed Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
title_sort Synthesis of oxadiazole-coupled-thiadiazole derivatives as a potent β-glucuronidase inhibitors and their molecular docking study
publishDate 2019
container_title Bioorganic and Medicinal Chemistry
container_volume 27
container_issue 14
doi_str_mv 10.1016/j.bmc.2019.05.049
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066996057&doi=10.1016%2fj.bmc.2019.05.049&partnerID=40&md5=ecd950b1a53d346832bbb97fc0a2db8b
description A new series of oxadiazole with thiadiazole moiety (6–27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard D-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition. © 2019 Elsevier Ltd
publisher Elsevier Ltd
issn 09680896
language English
format Article
accesstype
record_format scopus
collection Scopus
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