Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies

In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric...

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Main Authors:	Rauf, Abdul, Shahzad, Sohail Anjum, Bajda, Marek, Yar, Muhammad, Ahmed, Faiz, Hussain, Nazar, Akhtar, Muhammad Nadeem, Khan, Ajmal, Jończyk, Jakub
Format:	Article
Language:	English
Published:	Elsevier Ltd 2015
Subjects:	Q Science (General)
Online Access:	http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf

id	ump-9307
recordtype	eprints
spelling	ump-93072018-04-19T02:39:43Z http://umpir.ump.edu.my/id/eprint/9307/ Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub Q Science (General) In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53±0.027, 8.93±0.027, 12.96±0.13, 15±0.098, 18.9±0.027 and 19.7±0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21±0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83±0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns. Elsevier Ltd 2015 Article PeerReviewed application/pdf en http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf Rauf, Abdul and Shahzad, Sohail Anjum and Bajda, Marek and Yar, Muhammad and Ahmed, Faiz and Hussain, Nazar and Akhtar, Muhammad Nadeem and Khan, Ajmal and Jończyk, Jakub (2015) Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies. Bioorganic & Medicinal Chemistry, 23 (17). pp. 6049-6058. ISSN 0968-0896 http://dx.doi.org/10.1016/j.bmc.2015.05.038 doi: 10.1016/j.bmc.2015.05.038
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Malaysia Pahang
building	UMP Institutional Repository
collection	Online Access
language	English
topic	Q Science (General)
spellingShingle	Q Science (General) Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
description	In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53±0.027, 8.93±0.027, 12.96±0.13, 15±0.098, 18.9±0.027 and 19.7±0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21±0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83±0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns.
format	Article
author	Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub
author_facet	Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub
author_sort	Rauf, Abdul
title	Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
title_short	Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
title_full	Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
title_fullStr	Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
title_full_unstemmed	Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
title_sort	design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: structure activity relationship and molecular modeling studies
publisher	Elsevier Ltd
publishDate	2015
url	http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf
first_indexed	2023-09-18T22:07:45Z
last_indexed	2023-09-18T22:07:45Z
_version_	1777414821978832896

Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies

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