Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies

By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecul...

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Published in:RSC ADVANCES
Main Authors: Khan, Farhan Mahmood; Abbasi, Muhammad Athar; Rehman, Aziz-ur; Siddiqui, Sabahat Zahra; Butt, Abdul Rehman Sadiq; Raza, Hussain; Hassan, Mubashir; Shah, Syed Adnan Ali; Shahid, Muhammad; Kim, Song Ja
Format: Article
Language:English
Published: ROYAL SOC CHEMISTRY 2024
Subjects:
Online Access:https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001229396900001
author Khan
Farhan Mahmood; Abbasi
Muhammad Athar; Rehman
Aziz-ur; Siddiqui
Sabahat Zahra; Butt
Abdul Rehman Sadiq; Raza
Hussain; Hassan
Mubashir; Shah
Syed Adnan Ali; Shahid
Muhammad; Kim
Song Ja
spellingShingle Khan
Farhan Mahmood; Abbasi
Muhammad Athar; Rehman
Aziz-ur; Siddiqui
Sabahat Zahra; Butt
Abdul Rehman Sadiq; Raza
Hussain; Hassan
Mubashir; Shah
Syed Adnan Ali; Shahid
Muhammad; Kim
Song Ja
Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
Chemistry
author_facet Khan
Farhan Mahmood; Abbasi
Muhammad Athar; Rehman
Aziz-ur; Siddiqui
Sabahat Zahra; Butt
Abdul Rehman Sadiq; Raza
Hussain; Hassan
Mubashir; Shah
Syed Adnan Ali; Shahid
Muhammad; Kim
Song Ja
author_sort Khan
spelling Khan, Farhan Mahmood; Abbasi, Muhammad Athar; Rehman, Aziz-ur; Siddiqui, Sabahat Zahra; Butt, Abdul Rehman Sadiq; Raza, Hussain; Hassan, Mubashir; Shah, Syed Adnan Ali; Shahid, Muhammad; Kim, Song Ja
Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
RSC ADVANCES
English
Article
By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecules demonstrated their potent mushroom tyrosinase inhibition relative to the standard used. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c, inhibited mushroom tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant K-i calculated from Dixon plots for this compound was 0.016 mu M. The computational study was also consistent with the experimental results and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to mushroom tyrosinase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for the diseases associated with the over-expression of this enzyme.
ROYAL SOC CHEMISTRY

2046-2069
2024
14
23
10.1039/d4ra01063a
Chemistry
gold
WOS:001229396900001
https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001229396900001
title Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
title_short Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
title_full Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
title_fullStr Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
title_full_unstemmed Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
title_sort Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies
container_title RSC ADVANCES
language English
format Article
description By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecules demonstrated their potent mushroom tyrosinase inhibition relative to the standard used. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c, inhibited mushroom tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant K-i calculated from Dixon plots for this compound was 0.016 mu M. The computational study was also consistent with the experimental results and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to mushroom tyrosinase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for the diseases associated with the over-expression of this enzyme.
publisher ROYAL SOC CHEMISTRY
issn
2046-2069
publishDate 2024
container_volume 14
container_issue 23
doi_str_mv 10.1039/d4ra01063a
topic Chemistry
topic_facet Chemistry
accesstype gold
id WOS:001229396900001
url https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001229396900001
record_format wos
collection Web of Science (WoS)
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