Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations

Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations

The present study involves the synthesis of bisindolylmethane-hydrazone hybrids, 1-30, in a three-step reaction sequence, followed by evaluation against β-glucuronidase enzyme. The IC50 values for the potent compounds were in the range from 0.10 to 83.50 μM. Compound, a trihydroxy analog was found t...

Full description

Bibliographic Details
Published in:RSC Advances
Main Author: Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
Format: Article
Language:English
Published: Royal Society of Chemistry 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84954148937&doi=10.1039%2fc5ra19513f&partnerID=40&md5=49d79b871596792e0ca826baf1620051
id 2-s2.0-84954148937
spelling 2-s2.0-84954148937
Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
2016
RSC Advances
6
4
10.1039/c5ra19513f
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84954148937&doi=10.1039%2fc5ra19513f&partnerID=40&md5=49d79b871596792e0ca826baf1620051
The present study involves the synthesis of bisindolylmethane-hydrazone hybrids, 1-30, in a three-step reaction sequence, followed by evaluation against β-glucuronidase enzyme. The IC50 values for the potent compounds were in the range from 0.10 to 83.50 μM. Compound, a trihydroxy analog was found to be the most potent derivative, having an IC50 value of 0.10 ± 0.001 μM. Molecular docking revealed that the active compounds could fit perfectly into the binding groove of β-d-glucuronidase. The presence of hydroxyl groups on the aromatic side chain proved to be the single most important factor that contributed toward the inhibitory potential of these compounds. On the other hand, the imino group of the hydrazone linkage displayed interactions with the side chain carboxyl oxygen (Oε2) of Asp207. The high inhibitory potential of these compounds could be associated with these strong hydrogen bonds. Structures of all the synthesized compounds were confirmed using modern spectroscopic methods. © 2016 The Royal Society of Chemistry.
Royal Society of Chemistry
20462069
English
Article
author Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
spellingShingle Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
author_facet Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
author_sort Taha M.; Ismail N.H.; Imran S.; Anouar E.H.; Ali M.; Jamil W.; Uddin N.; Kashif S.M.
title Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
title_short Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
title_full Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
title_fullStr Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
title_full_unstemmed Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
title_sort Identification of bisindolylmethane-hydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations
publishDate 2016
container_title RSC Advances
container_volume 6
container_issue 4
doi_str_mv 10.1039/c5ra19513f
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84954148937&doi=10.1039%2fc5ra19513f&partnerID=40&md5=49d79b871596792e0ca826baf1620051
description The present study involves the synthesis of bisindolylmethane-hydrazone hybrids, 1-30, in a three-step reaction sequence, followed by evaluation against β-glucuronidase enzyme. The IC50 values for the potent compounds were in the range from 0.10 to 83.50 μM. Compound, a trihydroxy analog was found to be the most potent derivative, having an IC50 value of 0.10 ± 0.001 μM. Molecular docking revealed that the active compounds could fit perfectly into the binding groove of β-d-glucuronidase. The presence of hydroxyl groups on the aromatic side chain proved to be the single most important factor that contributed toward the inhibitory potential of these compounds. On the other hand, the imino group of the hydrazone linkage displayed interactions with the side chain carboxyl oxygen (Oε2) of Asp207. The high inhibitory potential of these compounds could be associated with these strong hydrogen bonds. Structures of all the synthesized compounds were confirmed using modern spectroscopic methods. © 2016 The Royal Society of Chemistry.
publisher Royal Society of Chemistry
issn 20462069
language English
format Article
accesstype
record_format scopus
collection Scopus
_version_ 1812871801979535360

Similar Items